In 79 A.D., Milo, a slave turned gladiator, finds himself in a race against time to save his true love Cassia, the beautiful daughter of a wealthy merchant who has been unwillingly betrothed to a corrupt Roman Senator. As Mount Vesuvius erupts in a torrent of blazing lava, Milo must fight his way out of the arena in order to save his beloved as the once magnificent Pompeii crumbles around him.

Picking up immediately after the events in Resident Evil: Retribution, Alice is the only survivor of what was meant to be humanity's final stand against the undead. Now, she must return to where the nightmare began - The Hive in Raccoon City, where the Umbrella Corporation is gathering its forces for a final strike against the only remaining survivors of the apocalypse.