Nobunaga Oda has come back to unlife as the Demon Lord, and Samanosuke Akechi is there to stop him. As the final battle begins, a portal suddenly whisks Samanosuke away. Present day Paris suddenly gets a surprise when hordes of demons lay assault to the peaceful city. Jacques Blanc desperately fights alongside his fellow French soldiers, but they are no match for the fiends. Strangely enough, Samanosuke appears and slices the demons to pieces.

Takeshi Kaneshiro returns as Samanosuke Akechi, the hero of the original Onimusha. Demon Siege also marks the arrival of Hollywood star Jean Reno as soldier Jacques Blanc. Now, the two heroes must fight together and take you on an epic adventure that goes beyond the boundaries of space and time.