Tooki Yobigoe is a direct sequel to Mamono Hunter Yōko: Makai kara no Tenkōsei, continuing where the story of the previous game left off. Yohko, Shoma and Setsuna are attacked by demons on the flying ship, and have to use their recently found powers to fend them off. As opposed to the previous game, where Shoma was the protagonist, Yohko is the player character in the sequel.

Gameplay-wise, the puzzle-less Japanese adventure format is further utilized. Verb commands must be selected from a menu and sometimes combined with objects or character names for interaction. It is often necessary to repeat commands several times to trigger the next event.