After Whistler is killed by the police, Blade joining forces with two vampire hunters, part of a group called the Nightstalkers, as they tackle the powerful and ruthless villain Danica Talos (Posey), her brother Asher (Rennie) and her minion Grimwood (Triple H). After harvesting the superior blood of the ancestor of all modern vampires, Talos has resurrected the man now known as "Drake" (notice the modernization of the Dracula name) from a century-long sleep in the hopes of finally getting world control for all vampires. Blade, along with the Nightstalkers must unleash a virus that will kill all vampires, but only are given one chance to make it work.

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