The Mad Doctor, whom Mickey and Sonic defeated in the first game, mysteriously returns to the Wasteland, despite having been supposedly blown up in the first game. He claims to have realised the error of his ways, and offers to work with Oswald The Lucky Rabbit and Manic the hedgehog and the other residents of Wasteland to repair the damage recently caused by earthquakes in order to make amends. Giving him the benefit of the doubt, Oswald agrees. However, not long after accepting the Mad Doctor's help, the Wasteland begins to suffer even more damage than before. Becoming suspicious that the Mad Doctor is not keeping his side of the bargain, Gus the Gremlin, Oswald's friend and advisor, and Ortensia, Oswald's girlfriend, and Manic the hedgehog; Sonic's brother and second in command decide to contact Mickey Mouse, who saved the Wasteland in the first game, to ask for his help along with Team Sonic. They do so, and Mickey, climbing through the same mirror that he ventured through in the first game, retrieves his magical paint-and-thinner-spraying paintbrush from Yen Sid's workshop, after having it confiscated at the end of Epic Mickey. With Gus's help, Mickey, Sonic and friends returns to the Wasteland to assist in uncovering the truth behind the Mad Doctor's supposed reformation, teaming up with Oswald along the way.
Our Heroes later discover that the Mad Doctor has been using his offer of help as a premise to release his new creations "Blotworx" (a mixture of the Blotlings and Beetleworx from the original Epic Mickey) into the Wasteland.. Realising his mistake, Oswald proceeds to assist Mickey and Sonic in taking down the Mad Doctor once again.
- Unlike the first film, Everyone from Team Sonic joins in the battle this time
- Guest Stars: Hinata, Wendy, Aki Uzumaki, Kushina, Erza, Sora, Kairi and Riku
- Past characters from old Sonic games will part along with the characters from the Sonic cartoons (Sonic Satam and Adventures of Sonic the hedgehog) like the first one
- This a Musical game, so songs from outside of Disney will be used for Sonic and his friends
- Prescott, a gremlin joins the Team to help Tails in his workshop. The request for Prescott join Team Sonic was made by Hinata as she feels sorry for the accused Gremlin.