Team Innocent: The Point of No Return is an adventure game with action elements. The game consists of three missions. The player controls Saki most of the time, but other girls temporarily become available as playable characters as well. The heroine must explore a large location, collecting items and solving a few puzzles on the way. The young women can also find and equip various weapons, from pistols to axes. The player can choose one of the four action modes: punching, kicking, shooting, and (in specific instances only) jumping. The girls are navigated from third-person perspective on pre-rendered backgrounds with constantly changing camera angles, similarly to Alone in the Dark games, except for the protagonists being sprites and not 3D models. The game has a few anime-style cutscenes and voice-overs for dialogues.

The events of the game are set in the future. The Galactic Police discovers that a scientist named Cronus has conducted genetic experiments on human beings. The police chief rescues three little girls, each one of whom bears the traces of these experiments. Fast-forward fifteen years: the three young women - Saki, Lilis, and Ariel - now work for the Galactic Police, determined to find out the truth about their origins and the nature of experiments. They are sent on three dangerous missions - missions they might not survive...