"Persona: Trinity Soul" is set ten years after the events of "Shin Megami Tensei: Persona 3," in the fictional city of Ayanagi. The story revolves around the Kanzato brothers: Shin, Jun, and Ryo. Shin, the eldest, returns to Ayanagi after a long absence to reunite with his younger brothers following the death of their parents. The city is plagued by mysterious incidents known as "Reverse," where individuals lose their personalities and become empty shells. These events are linked to the emergence of Personas, manifestations of a person's inner self, which are now appearing in adults—a phenomenon previously thought to occur only in adolescents.

Shin, now a detective, investigates these strange occurrences alongside his colleague, Megumi Kayano. As the brothers delve deeper into the mystery, they discover that their family is connected to the origins of the Reverse incidents. Jun, the middle brother, begins to exhibit strange behavior, while Ryo, the youngest, harbors secrets of his own. The narrative explores themes of identity, memory, and the bonds between siblings as the brothers confront their past and the truth behind their parents' deaths.

The series introduces a unique take on the Persona concept, focusing on the psychological and emotional struggles of its characters. The Kanzato brothers must navigate their relationships while uncovering the dark forces at play in Ayanagi. The story intertwines personal drama with supernatural elements, creating a complex narrative that examines the consequences of wielding Personas and the impact of unresolved trauma. The series maintains a balance between character-driven storytelling and the overarching mystery, culminating in a resolution that ties together the brothers' fates and the city's enigmatic events.