Blade is moving through an abandoned building somewhere in the city. It looks like a heroine den, junkies sprawled out on torn couches, hookers taking Johns to rooms with stained mattresses on the floor. He’s descending down a stair case and into the dank basement. It’s pitch dark, but Blade keeps moving, sliding his sunglasses to the top of his head. Sword out, he wades through knee-deep waters, corpses resembling those from the upper floors are floating on the surface, their necks torn open. Ahead, Blade finds a secret door.

It’s a vampire den, and according to the chatter with his team over his earpiece, it’s one of the last.

As he turns over coffins and uncovers cells, vampires emerge in force. He goes to work slicing them up, his team yelling for him to release the canister and run. He ignores them, choosing hand to hand combat instead. The fight is in his favor, but one imposing vampire puts up an extraordinary resistance. In an onslaught of the undead with this super vamp in the lead, Blade gets overrun, his sword goes missing, and he struggles to get free. Blade has lost a step or two in his years on the hunt, yet he’s grown more ferocious. He bites his way through the horde. Fleeing the building, he tosses the canister behind him. He sees the big bad vampire running the opposite direction.

A substance permeates through the aged structure, killing some vampires while curing the others. The drugees and hookers run in a panic when a fire starts. Blade watches the building burn, vampires and humans getting caught in the flames. As the police pull up, Officer Sterling Deacons spots Blade and shouts for him to stop. Blade hisses, wipes the blood from his mouth, and runs into the night.

Back at Blade HQ, the team tells Blade the front-line combat tactics are no longer necessary. They can send drones in to drop the canisters. Blade says he prefers to make sure the job gets done in person. His lead hematologist/epidemiologist, Jessica Winters, lets him know the dangers of being around the substance could turn Blade human, which wouldn’t do him any good in the field.

She also tells him their work may almost be done. It’ll be time soon enough where he’ll be the last vampire, time when he can finally take the cure himself. Blade thinks she’s a fool and that the vampires are just getting better at hiding. She hands him his serum. We see him toss the vials into the alley on his way out.

It’s a late night at the police station and Deacons is looking through a few case files, all about similar attacks on drug dens and brothels going up in flames, ashen corpses left behind. Another detective brings a young woman over to Deacons, mumbles something about a Dracula loving idiot, and walks away laughing. The woman, Asami, says she and her friends are recovering addicts, but some of her friends are struggling, falling back into old habits and roaming the streets looking for drugs. Some have disappeared.

While Deacons flips through grainy photos of Blade, Asami talks about her friends being lured by the same types of people recently. She says it sounds crazy, but they think these people are vampires who are creating these places to bring in victims. She was told that Deacons might actually believe their story. Deacons is distracted. He looks at his latest photo of Blade he took with his phone, seeing that he’s missing his sword. Deacons takes off, telling Asami he’ll stay in touch.

Blade returns to the building as the fire and police are leaving. When he goes back in for his sword, Officer Deacons is there waiting for him. He says he just wants to talk. He knows about what he’s been doing, or thinks he knows, and has questions. Blade entertains the officer at first, but what appears to be wearing patience over his missing sword is actually Blade’s uncontrollable hunger. He tells the officer vampires are very real and showcases his fangs, threatening to bite Deacons. Deacons begs for his life, says he can help Blade’s cause, and Blade lets him live.

Asami is lurking in an alley, watching a drug deal from afar. Then a shadowy figure comes in to speak with the buyer. It’s the big vampire from the first den. He pulls out a sample of some undefined substance, scribbles something on a note, and hands them both over. When the figure leaves, Asami intercepts and takes the note. On it is an address.

Jessica checks in on Blade at HQ. He’s obviously ill and she asks him to be honest with her. She’s found his discarded vials; she knows he hasn’t been taking them. He says the serum isn’t working anymore, and he’s losing his fight against the hunger. She tells him he doesn’t have to endure the virus anymore. She can cure him and still win the war. He’s made vampires his focus for so long he hasn’t allowed himself to live a human life, one with real relationships. There’s a subtle connection between them. Blade says he doesn’t think he’s built for love. She says that can’t be true. He’s part vampire, but he’s not dead inside. He can still have another life.

Deacons shows up at Blade’s HQ, Asami in tow. He confesses to following Blade after the night at the burned-down building, but he’s not here to arrest him. Asami came to him with information that he feels would be better utilized by Blade and crew. The cops wouldn’t know how to handle vampires; he just wants to help where he can, but if they go after another den, Deacons wants to be kept in the loop.

He leaves Asami behind, and she explains to Blade the process of the den creations and that she believes all her friends were killed by vampires. Blade asks how she’d know that, and she shows him her bite. She’s a vampire too. He asks if she has recently fed, and she says she’s fine. She works at a pet store that specializes in snakes and they get lots of rats. Sometimes their shipments are missing a few.

Asami explains her plan to uncover new dens, but first they need to confirm the address is what she expects. Blade says he’ll go alone. Asami says she wants to fight. She wants revenge for her friends. The pair face off as a test of her skills. She doesn’t know anything about swords, but her martial arts skills are a match for Blade’s. She says she was an army brat whose parents were both highly-trained combatants, and she was in a lot of fights when she was young, many she started on purpose.

With the exhibition over, Jessica says neither of them need to engage the vampires and shoves a drone into Blade’s hands. She says he just needs to send it in through a window. It can show him a visual of the inside, and if there’s vampires he just presses a button and it’s game over. Asami wants to go along to see if her friends are inside.

Blade reluctantly agrees to both. At the location, a boarded-up assembly plant in a rundown industrial district, Deacons is waiting to help. Blade sends in the drone. Inside the scene is familiar, drugs on the surface, and beneath that vampires.

Asami talks to Blade about being a vampire, and the possibility that not all vampires are bad. He’s not bad. She’s not bad. Maybe this isn’t a war so much as a pandemic, and what if there are others that could help them cure who wants to be cured, while managing their own downsides of the illness. Deacons wonders if the positive properties of the virus could be used to help cure human illnesses, then the person could be given the vampire cure.

Blade says he’s willing to distribute the cure instead of killing, but he’s not willing to make more, and leaving one vampire to roam the earth is like leaving the nuclear codes on a post-it next to the switch. Via the drone, Blade sees the head vampire. He puts the drone controls down and says he’s going in. “That guy has my sword. Be right back.” Blade runs into the plant. Asami and Deacons follow.

They fight their way through the building, styles slightly different, Asami showing more speed and strength than before. She’s more than she seems. Deacons picks up the slack. Blade is feral, chewing through vampire and a spattering of recent victims. When they get to the leader, Blade is ready to fight, but Asami wants to talk, and so does the leader. His name is Khan, and he says he’s the last pure blood. He’s not trying to dominate the world or anything sinister. He just doesn’t want to see his species die. Seeing Blade’s fangs dripping with blood, he questions if Blade really wants that as well. Asami suggests maybe a truce can be made, that maybe vampires don’t have to be seen as evil. Maybe they can use their power to protect humans, not kill them. Khan even returns Blade’s sword to show his willingness to the idea. Blade isn’t having it though, and he attacks Khan. Asami jumps in to separate them, and ends up fighting both. Khan manages to get away, and the group reconvenes at HQ

Blade is furious. He wants to know just who Asami is. He knows she’s lying about being a turned vampire. She says he’s right. The bite she showed him was makeup. Her parents were turned vampires as part of an army experiment and she was born after like blade. Jessica examines Asami, confirming that the virus is more engrained in her DNA. She has enhancements like strength and speed, better night vision and enhanced senses, and quick healing. She doesn’t need to drink blood to live, (the eating rats story was a lie, she saw it on Interview with a vampire) she’s immune to daylight, garlic, and silver, and she can’t pass the virus to others. She’s a perfect warrior.

She backs up her claim that there’s something useful about the vampire virus and they shouldn’t just kill them all. Deacons agrees, and one of the technicians catches him trying to steal some of Asami’s blood. He runs off. There’s more time with Jessica and Asami bonding, and Jessica is trying to connect with Blade, especially when he disappears and comes back covered in blood. She doesn’t know what or who he’s feeding on. She thinks it’s finally time for him to take the cure, before it’s too late. Deacons contacts them about finding a new den. Asami says she’ll go along with whatever Blade wants to do.

At the new den Deacons isn’t waiting outside. Blade sends in the drone like before, but there aren’t any junkies inside and the vampires aren’t sleeping. They’re feeding, growing stronger. Blade watches them and his fangs extend. His eyes are wild. His finger is on the button that drops the canister, but he can’t push it. He wants what they’re having, and then he sees something else.

The ones who aren’t sucking down blood are arming themselves, waiting, and he hears Deacon’s voice inside. He says Blade and Asami are coming and that they’ll get them, but not to kill him, to remember their deal. Blade is enraged. Rather than pushing the button, he goes in sword flying. He tears through the vampires, cutting them to pieces, and despite the readied trap, Blade and Asami are victorious. They search for Deacons to punish him for his betrayal, but they only find a phone. Deacons is on the line.

He says his son is dying from cancer and all he ever wanted was to save his son, but after hearing Blade’s take on vampirism, he knew it was going to be difficult to get help. He worked a deal out with Khan who would trap them there while he got Asami’s blood and the vampire cure from their headquarters. Blade says Khan isn’t there and they all realize where he is.

At Blade HQ, Khan has Jessica and the team hostage. Deacons has his gun drawn to shoot any of the team that tries to run. Khan makes a final plea to Blade to consider Asami’s idea of a truce. Asami says Khan’s threat of violence isn’t the way to achieve peace. Khan says that’s always been the way to peace. People have to die so others may live. He bites Jessica and Blade and Asami both attack. Khan is too powerful for both Asami and Blade, but Deacons shoots Khan which temporarily throws him. Blade sees Jessica suffering, and knows he can’t beat Khan. As a last resort, Blade tosses a canister into the middle of the fight, and the ‘cure’ is set loose on them all. Blade and Asami are both coughing on the fumes. While Khan screams turning to ash, Blade falls to the floor. His eyes change and his fangs disappear. His vampire side is being erased. He looks at Jessica for the first time with totally human eyes and smiles, but Khan reaches for Blade and tears out his throat. They both die.

Deacons helps Jessica stop the bleeding. He’s begging her forgiveness as she holds Blade’s hand. Through the smoke, Asami’s wounds are healing.

Over a montage of Asami training with a sword, driving Blade’s black charger through the streets of the city, and fighting random foes, she says, “Maybe Eric was right. Vampires are dangerous and keeping them alive is a mistake. If more exist, I’ll kill them and cure them where I find them, but whatever I am, I’m using it for good. There’s evil out there that can’t be cured with a vaccine. It needs to be fought in other ways. Sometimes it needs the fist, the gun. Sometimes, it needs the blade.”