Persona: Trinity Soul takes place ten years after the end of Persona 3. It is set in Ayanagi City, a city located near the Sea of Japan, where the police force is investigating several cases involving a mysterious illness called the Apathy Syndrome. Ten years ago, Ayanagi city had been subjected to a severe earthquake, which the city has since recovered from.
In the midst of the crisis, two brothers named Shin and Jun Kanzato move back to Ayanagi to see their elder brother Ryō, who is now the Superintendent of the Ayanagi City Police. It has been ten years since the three siblings last met with each other.
It was said that the mysterious incidents in Ayanagi City were linked to covert testing conducted under Keisuke Komatsubura's watch, which tried to locate all known Persona users and find the strongest by weeding them out via Persona experiments before it was disbanded.