The year is 1582 and 10 years have passed since the events that unfolded in Onimusha 2 Samurai's Destiny . The stage is set at the burning Honnoji Temple , as the famous Onimusha warrior Samanosuke Akechi (Takeshi Kaneshiro) continues to fight the demons in his path. The moment has finally arrived for Samanosuke to confront the true enemy that has eluded him until now, the undying Nobunaga Oda. Unfortunately before the long-awaited final battle begins, Samanosuke is suddenly engulfed in a whirlpool of light and disappears.

The year is 2004. A peaceful French metropolis is suddenly attacked by demons. In the blink of an eye, the city is transformed into a hellish sea of blood as Genma demons slaughter civilians and soldiers one by one. Within this pit of darkness appears one man who stands up against the Genma demons, Jacques Blanc (Jean Reno). As a member of the French army, Jacques is deployed to the nightmarish scene only to discover himself amid a plague of horrific enemies that are beyond any one's imagination. An ancient samurai warrior unexpectedly appears to help him defend the helpless city. As they cooperatively fight off the demons, Jacques is caught in a mysterious vortex and vanishes to feudal Japan , leaving the warrior behind in modern day France

Why has Samanosuke appeared in present day Paris and Jacques in feudal Japan ? What fate awaits these two men? The fierce and bloody battle is unfurled as the beginning of the final Onimusha chapter unfolds.