A mysterious epidemic called Infel Pira Dependency (IPD) has been driving Reyvateils insane and killing them at the floating land of Metafalss. Croix, a young knight from the Church of Pastalia, is sent to contain the epidemic. However, many more challenges await, which lead him to unraveling the mysteries of the planet Ar Ciel and seek the legend handed down by the people of Metafalss: the lost Song of Metafalica.

Ar Tonelico 2 marks a new approach to the RPG genre by seamlessly combining simulation with role-playing. Gamers can not only synthesize weapons and items, but now design their character's characteristics through virtual interaction. Also past events will intersect with future game play as well as the outcome of the game.