Based on the Gothic mental institution located north of Boston, in Danvers, Massachusetts, Lost Souls of the Witches' Castle is a story within a story. Dana Etheridge and Nick DeSantis meet on the grounds of the closed facility. Dana is an RN who did her psychiatric training there ten years before and Nick is a photojournalist writing a book about Danvers State.

Within moments of meeting, they're drawn to each other. With the help of Hannah, Dana's grandmother, and a journal written by a former patient placed there in 1919, they discover their own destiny, the connection of their souls and the powerful effect of love.