A Heart is a major plot point in Epic Mickey. Any Disney character who is loved by many has a heart of their own. All Disney characters who have a heart reside in the Toon World. Otherwise, once forgotten or retired, they are sent to the Wasteland and their heart disappears. The game's novelization states that people who lack Hearts feel hollow, abandoned and empty. Mickey Mouse has the most powerful heart of all, and the villains (by far mostly the Shadow Blot) want to use it to escape the Wasteland.
The Mad Doctor attempts to extract Mickey's heart at the beginning of the game to help the fake Shadow Blot escape Wasteland, but fails.
Near the end of the game, after Mickey has redeemed or defeated the fake Shadow Blot, the real Shadow Blot is accidentally unleashed from the Jug on Mickeyjunk Mountain, who then holds Gremlin Gus and Oswald hostage, and will release them if Mickey gives up his own heart. The deed is done, unfortunately, and now the trio must defeat the Shadow Blot from the inside.
Once Mickey destroys all the Bloticles inside the Blot, his heart is released, only for Oswald to grab it. After realizing that Mickey deserves it more than him, Oswald allows it to go back inside of Mickey's body, before unleashing a barrage of fireworks to destroy the Blot once and for all.
In Epic Mickey 2: The Power of Two, the Mad Doctor plans to become famous again by creating an artificial heart through the toons. Utilizing a television transmitter similar to the one Gus constructs in the opening of the game, the Mad Doctor broadcasts his own television show to the Cartoon World, "The Wonderful World of Evil", and is hoping the ratings there will give him a heart again. To become a Toon once more, he pumps the Guardians from the ground beneath Wasteland in an effort to try and harness their power and get revenge on Wasteland by leaving it in an inert state (his machines were the cause of the surge in quake activity). And with the Brush, he would move to the top of the Disney Villain hierarchy.