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.

Life for former United Nations investigator Gerry Lane and his family seems content. Suddenly, the world is plagued by a mysterious infection turning whole human populations into rampaging mindless zombies. After barely escaping the chaos, Lane is persuaded to go on a mission to investigate this disease. What follows is a perilous trek around the world where Lane must brave horrific dangers and long odds to find answers before human civilization falls.

Grief-stricken mother Christine Collins (Angelina Jolie) takes on the L.A.P.D. to her own detriment when it tries to pass off an obvious impostor as her missing child.