In the game, Neku Sakuraba and his allies are forced to participate in a game that will determine their fate. The battle system uses many of the unique features of the Nintendo DS, including combat that takes place on both screens, and attacks performed by certain motions on the touchscreen or by shouting into the microphone. Elements of Japanese youth culture, such as fashion, food, and cell phones, are key aspects of the missions.

A boy named Neku wakes up in a crowded intersection of Shibuya in the heart of Tokyo – alone and unaware of how he got there. Then, he receives a text message: “Clear this mission...or face erasure.” With that, Neku is thrust into a life-or-death game that sends him scrambling down streets paved with one riddle after another.