The full plot runs from the Purge to a raid on a corporate tower, and it ends with Michael missing again.
Six months after the earlier film, the public learns that vampires and Lycans exist. A human program to study them becomes the Purge, and Selene and Michael are caught in it. Selene goes into cryogenic suspension, and about twelve years later she breaks out of the facility and takes a young girl with her. The girl is her hybrid daughter, Eve.
A vampire named David takes the pair to his coven. The Lycans attack that coven, and Selene fights a huge Super Lycan called Quint. David is badly wounded, and Selene saves him with her blood. It then emerges that David's father, Thomas, had handed Eve to the Lycans in an attempt to stop the attack.
Selene and Detective Sebastian (Michael Ealy) trace the Lycans to Antigen, a company run by Lycans posing as humans. Its head, Dr. Jacob Lane (Stephen Rea), wants Eve's DNA to strengthen the Lycan race. Selene, Sebastian and David raid the Antigen building, and inside Selene finds Michael in a cryogenic tank and frees him.
She has to leave him as he thaws, because the Lycans are about to take Eve. Selene lures Quint into his weaker human form and kills him with a silver grenade, and Eve kills Lane. When the group goes back to Michael's tank, it is empty.