In the aftermath of their ordeal through the Umbrella Corporation's genetic research facility, the surviving members of the S.T.A.R.S. attempt to warn the world about the conspiracy to create terrifying biological weapons. But the conspiracy is far from dead, as they learn when they are declared outlaws by the very people who trained them. Forced to go underground, the S.T.A.R.S. resolve to battle the conspiracy on their own, determined to seek out and stop Umbrella's experiments wherever they may be.
Combat medic and biochemist Rebecca Chambers, the sole survivor of Bravo Team, joins a new S.T.A.R.S. strike force when rumor comes of another Umbrella experiment: hidden beneath the rocky cliffs of Caliban Cove, Maine, someone is building an army of the undead. Within a sinister lighthouse, through a complex maze of sea caves, inside the shell of a sunken shipwreck, the S.T.A.R.S. must battle more unspeakable horrors and stop a madman from unleashing the biohazard upon the world.