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.

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.