In the sprawling metropolis of Ryme City, a place where humans and Pokémon coexist in harmony, the story begins with the disappearance of ace private detective Harry Goodman under mysterious circumstances. His estranged son, Tim Goodman, arrives in the city to investigate his presumed death. Tim is a former Pokémon trainer who has given up on his dreams, working a mundane job far from the excitement of Ryme City. Upon entering his father's apartment, Tim encounters Harry's former Pokémon partner, a wise-cracking, amnesiac Pikachu that only he can understand. Unlike the typical electrifying creature of its kind, this Pikachu wears a detective hat and claims to be a brilliant sleuth.

Together, Tim and Pikachu embark on a twisting investigation through the neon-lit streets of Ryme City. They form an unlikely partnership, as Pikachu possesses key clues to the whereabouts of Tim's father, though his memory is jumbled and incomplete. The duo encounters a diverse cast of Pokémon, encounters humans with hidden agendas, and discovers a broader conspiracy that threatens the peaceful coexistence of the Pokémon and human worlds. They are assisted by a determined junior reporter named Lucy Stevens, who is accompanied by her Psyduck, as they delve deeper into the mystery. Their journey is fraught with action, danger, and the occasional hearty laughter, stemming from Pikachu's jocular demeanor and Tim's reluctant heroism.