The world in Rezel Cross is undergoing an awakening after a comet passes by. Beasts undergo rapid evolution and dormant abilities in humans start to manifest. Increased strength, faster reflexes and agility transform a small number of humans into super humans known as "rezel". While the world is in constant flux Isle, Lefia and three other heroes gifted with rezel powers begin their tale.

The game is split into 20 chapters and the heroes gain the powers of teleport, time pause, psycho kenesis, transformation and x-ray vision as they progress. In addition, the battles are in full 3D with an XMB like interface and the heroes get skill points to unlock new abilities and Rezel Arts as well as Hyper Rezels.

The game has character designs by Eiji Kandeda who also did character designs for Aquarion and a script written by the team who wrote Arc the Lad III & IV.