The year is 1929. America is threatened by a mysterious evil power. Pale green distortions in the sky, called "windows", spawn vicious monsters. Johnny Garland is a young man who has lost his family and his memory in a terrible accident. It turns out that he inherited a fortune from his father, but he is not interested in money, but in re-discovering his own past. For that reason, Johnny becomes a private investigator. He receives an assignment which involves capturing an escaped convict. During the investigation, Johnny meets Shania, a native American woman who works as a monster-hunter. From that point on, the destinies of the two are linked together...

This installment of the Shadow Hearts series utilizes almost the same gameplay system as Shadow Hearts: Covenant. The turn-based battles are once again controlled by the Judgment Ring: you must stop a spinning indicator on a colored segment of a ring in order to execute a successful attack. New in this game are combo attacks which the players can execute through special areas of the Judgment Ring.