Two years after the events that saved the planet from destruction, the world is still recovering from the calamity. Cloud Strife, a former mercenary and key figure in the planet's defense, is plagued by guilt over his past and a mysterious illness weakening the populace, known as "Geostigma." Withdrawing from his friends and the life of a hero, Cloud has chosen a solitary existence, running a delivery service and distancing himself from his former comrades who are now rebuilding the city of Midgar. However, his quiet life is interrupted by the appearance of Kadaj, Loz, and Yazoo, three enigmatic figures who seek to resurrect their fallen leader and threaten to unleash a new horror upon the world.

As the trio begins to terrorize the citizens in their search for their leader's remnants, Cloud is forced out of hiding and reluctantly steps back into the fray. His journey to save the planet yet again draws him into battles against monstrous creatures and confrontations with his own inner demons. Meanwhile, the children of the city are being abducted, and it becomes clear that the mysterious illness and the new threat are connected. To protect the future and find redemption for his past, Cloud must confront his fears and the specter of his old nemesis, gathering allies both old and new to face the emerging menace that could lead to the planet's ruin.