Prodigal Son is set primarily in New York City and follows the NYPD's Major Crimes Unit as they investigate unusual and often brutal murders. Malcolm Bright works as an unconventional criminal profiler alongside detectives Gil Arroyo, Dani Powell, and JT Tarmel, with medical examiner Edrisa Tanaka providing forensic support. Malcolm's greatest resource—and greatest psychological burden—is his father, Martin Whitly, a notorious serial killer imprisoned at Claremont Psychiatric Hospital. The Whitly family's wealth, secrets, trauma, and complicated relationships repeatedly become intertwined with the investigations.