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.

Dr. Adrian Helmsley, part of a worldwide geophysical team investigating the effect on the earth of radiation from unprecedented solar storms, learns that the earth's core is heating up. He warns U.S. President Thomas Wilson that the crust of the earth is becoming unstable and that without proper preparations for saving a fraction of the world's population, the entire race is doomed. Meanwhile, writer Jackson Curtis stumbles on the same information. While the world's leaders race to build "arks" to escape the impending cataclysm, Curtis struggles to find a way to save his family. Meanwhile, volcanic eruptions and earthquakes of unprecedented strength wreak havoc around the world.