故事从97年《最终幻想VII》结局两年之后开始，当人们以为世界已经和平之时，所谓的“星痕症候群”的病却开始四处蔓延，世界再度面临危机。同时曾经为拯救世界而战的英雄克劳德却与世隔绝孤独的生活着……
　　剧情叙述主角们打倒赛菲罗斯（Sephiroth），拯救星球免于巨大陨石的侵袭后两年，神秘的怪病「星痕症候群」在各地陆续传出病例。而主角克劳德（Cloud）在与爱莉斯（Aerith）死别后，便郁郁寡欢。某日突然出现了与赛菲罗斯有未知关联的神秘3人组，除了直接对克劳德造成威胁之外，还进行着一连串秘密的计划，将已回归各自生活的主角群们，再次的卷入风波中……

Two years have passed since the final battle with Sephiroth. Though Midgar, city of mako, city of prosperity, has been reduced to ruins, its people slowly but steadily walk the road to reconstruction. However, a mysterious illness called Geostigma torments them. With no cure in sight, it brings death to the afflicted, one after another, robbing the people of their fledgling hope.