After the events of the original Tales of Symphonia, when Lloyd Irving and his friends united the twin worlds of Tethe'alla and Sylvarant, chaos surfaced, based on the two planet's differences. The new world's climate went through many changes, with lakes becoming dry valleys and deserts turning into frozen wastelands, and the technological discrepancy between Sylvaranti and Tethe'allans led to a bloody conflict in global scale.

Players assume control of Emil Castagnier, a boy from the city of Palmacosta who had to watch his parents getting killed by Lloyd, the hero from the original adventure, during a battle that would be later known as the "Blood Purge". He parts in a journey for revenge and then meets Marta Lualdi, a girl who is being chased by Sylvaranti forces and the mysterious Richter Abend, whom he vows to protect from harm.

The game is controlled by the Wii Remote in combination with the Nunchuk controller and its gameplay can be divided into two parts: overworld exploring and battling. In the former, players can interact with non-playable characters and the environments or be confronted by enemies which activates the combat mode. Battles happen in real time; the player controls one of the up to four party members that are fighting, with the others being controlled by the game's AI or other players. New to the series is the inclusion of more than 200 different monsters that can be captured to fight alongside your other characters in battles.