The game begins in North America in the year 1929 and features two new main characters: a 16-year-old New Yorker named Johnny Garland, and a 21-year-old Native American woman named Shania, who has powers of fusion similar to Yuri and Kurando in the previous Shadow Hearts entries, although she is not a harmonixer. She makes pacts with spirits while Yuri and Kurando turned into demons. The story begins with Johnny, a private detective, being hired by a man named Gilbert to find one Marlow Brown. When Johnny finds the man, however, a mysterious 'window' opens, and from it emerges a monster. The rest of the game follows Johnny, Shania, and company as they attempt to uncover the truth about Gilbert and his plans.
Meanwhile in Brooklyn, a wanted criminal who was severely injured was being pursued by the police. He met a mysterious woman who rescued him by finishing off his pursuers with ease. Then, she healed his wounds with the 'Kiss of Malice.' Nobody knows what her intentions...
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