The vampires succeed in framing Blade for the killing of a human (a familiar being used as bait when posing as a vampire). Blade, now in the public’s eye and wanted by the FBI, is forced into hiding with his mentor, Abraham Whistler. A few days later, the FBI attack the hideout. During the siege, Whistler destroys the hideout after being mortally wounded, killing him in the ensuing explosion. The loss of his mentor allows Blade to be captured easily.
As the police prepare to hand Blade over to a group of vampires, Blade is rescued by Hannibal King and Abigail, Whistler’s daughter. The two head a group of vampire hunters called the Nightstalkers, formed by Blade’s mentor to assist him. Blade reluctantly joins the group after learning King was once a vampire. King and Abigail reveal that Danica Talos (Parker Posey), who was the vampire who bit King, has located and resurrected the ancient first vampire, Dracula (Dominic Purcell) (who is referred to as Drake throughout the film). Talos hopes that by resurrecting Dracula, he (Drake) will help save the vampire race and eliminate Blade. In his first confrontation with Blade, Drake shows a sort of affinity for the “Daywalker”, as they are both “honorable warriors” (somewhat ironically, while Drake is delivering his speech about honor, he is hiding behind a newborn baby he has taken hostage). During the beginning of the chaos, King is incapacitated by Drake.
Blade eventually learns of a bioweapon the Nightstalkers had created called Daystar. The weapon is capable of killing any and all vampires in a nearby area. However, there are two catches: The first is that Drake’s blood must be infused with the virus. As he is the first vampire, his DNA is still pure, which, infused with Daystar, will make it work to its maximum capacity. The second: the virus has a possibility of killing Blade, as he is a half-vampire.
Blade and Abigail learn of the vampire “final solution”, which involves several hundred human beings being kept alive in a comatose-like state in body bags. This keeps in line with vampires needing live food sources if the entire vampire race were to take over the world. Blade coldly has all of them killed, destroying their “final solution.”
The two return to find the Nightstalkers have been all but wiped out. The only exception is King, who has been kidnapped by Drake (disguised as Blade’s mentor, Whistler), who had also killed the rest of the Stalkers; and kidnaps a young girl named Zoe, the daughter of one of the Nightstalkers. Blade and Abigail have no choice but to rescue King from the Talos building where he had been chained and tortured for information, and where Drake also is hiding.
Meanwhile, King is tortured for information about Daystar. When this fails to get any information from him, Talos instead tells King that she will bite him again and leave him to feed on Zoe. Blade and Abigail eventually enter the building and the fighting begins. Abigail kills Danica Talos’ brother, Asher (Callum Keith Rennie) and King kills Jarko Grimwood (Triple H) while Blade engages Drake in a sword battle. In the end, Blade impales Drake with the Daystar arrow, which draws his blood and releases it into the air, killing all the nearby vampires, including Danica Talos. Drake dies after promising Blade a “parting gift.” The disease subsequently appears to kill Blade as well. The FBI later discover Blade’s body and call off their search. However, the corpse turns back into Drake’s at the morgue. The film ends with Blade driving off into the sunset to continue his war against vampires.
