Having escaped years of imprisonment, vampire warrioress Selene finds herself in a changed world where humans have discovered the existence of both Vampire and Lycan clans and are conducting an all-out war to eradicate both immortal species. Now Selene must battle the humans and a frightening new breed of super Lycans to ensure the death dealers' survival.

Famed monster slayer Gabriel Van Helsing is dispatched to Transylvania to assist the last of the Valerious bloodline in defeating Count Dracula. Anna Valerious reveals that Dracula has formed an unholy alliance with Dr. Frankenstein's monster and is hell-bent on exacting a centuries-old curse on her family.