Set in an ancient haunted landscape layered with Pueblo, Hispanic, and Anglo cultures, Taos Gothic begins with the disappearance of well-known Santa Fe historian Kate Isaacs while staying and doing research at the historic Mabel Dodge Luhan House in Taos. Isaacs' wife hires private investigator Fernando Lopez to find the missing woman.

At the Luhan House, now a bed and breakfast inn, Lopez learns that Isaacs walked out of her room during the night wearing only a nightgown and slippers. Employees and a local paranormal organization blame ghosts. They tell him the sprawling 100-year-old house is haunted by the ghosts of the famous people who stayed there, including Georgia O'Keeffe, Willa Cather, and D.H. Lawrence, as well as Mabel and her Native American husband, Tony.

The mystery deepens when a former lover of Isaacs turns up dead at a party Isaacs attended the night she disappeared. Isaacs is a suspect in the murder until it becomes clear that she has been kidnapped. Lopez teams up with Taos County Sheriff Hank Mathews after kidnappers contact Isaacs' wife and demand a ransom for her return. Their investigation leads them to a derelict A-frame in the mountains, where they find Isaacs' body and the bodies of two other people. Solving the murders takes them into a dangerous underworld of transients, paranormals, and psychopaths.