Set during World War I in a fantastical world of magic and creatures, the game takes place over a year after the original Shadow Hearts ended. Yuri, the main character is back, and he embarks on a new expedition with friends Gepetto and Kallen, a German female soldier. Yuri's morphing abilities have been weakened because he has been cursed by Nicholas, a member of a secret cult taking advantage of the war to fulfill their evil ambitions of ruling the world. Yuri and his companions must journey to find a cure for his curse and defeat the malevolent cult.