The climax unfolds in Viktor’s mansion during a Lycan assault. Selene, betrayed by Viktor, joins Michael and a pragmatic vampire named Kraven (Shane Brolly), though Kraven ultimately proves treacherous. Michael is bitten by both a vampire (Selene, inadvertently) and a Lycan, transforming into the first true hybrid. He gains Lycan strength and healing plus vampire fangs, speed, and resistance to sunlight.

She discovers that Michael carries a rare genetic trait—descended from the first immortal, Alexander Corvinus—that allows him to survive being infected by both vampire and Lycan strains. Lucian intends to create a hybrid army.

The protagonist, Selene (Kate Beckinsale), is a "Death Dealer"—a vampire assassin dedicated to eradicating Lycans. For centuries, she has believed the Lycans are savage beasts who slaughtered her family and now seek to destroy vampirekind. Her mentor, vampire elder Viktor (Bill Nighy), leads the coven from a subterranean mansion.