A group of vampires travels to the desert to resurrect Dracula (Dominic Purcell). After he's brought back to life, he's known as Drake, and he has new gifts, including the ability to exist in daylight. Then the vampires launch a campaign against their nemesis, Blade (Wesley Snipes), and his mentor, Whistler (Kris Kristofferson). Blade and Whistler's only hope is to team with the Nightstalkers, a group of human vampire hunters lead by Abigail (Jessica Biel) and Hannibal King (Ryan Reynolds).
For years, Blade has fought against the vampires in the cover of night, with the world above unaware of the brutal ongoing war. But now, after falling into the crosshairs of the FBI, he is forced out into the daylight where he is driven to join forces with a clan of human vampire hunters he never knew existed - The Nightstalkers. Together with Abigail (Jessica Biel) and Hannibal (Ryan Reynolds), two deftly trained Nightstalkers, Blade follows a trail of blood to an ancient creature that is hunting him...the original vampire, Dracula.