The basic premise of the show focuses on Mickey Mouse and his friends operating a dinner theater club in downtown ToonTown.

The show also featured some cameos by characters created for other television cartoons such as Pepper Ann and theme park attractions like The Haunted Mansion, but these appearances were few and far between.

Each episode focuses on a story involving Mickey and his associates facing an issue during an evening's operation of the club, and their efforts to overcome it – the most common plot for episodes involves the group dealing with a serious problem caused by Pete in his attempts to shut down the club and use it for his own gains.

Roberts "Bobs" Gannaway and Tony Craig aimed to have the series reintroduce Disney characters to a new generation who were only familiar with them via marketing and "homogenized theme-park figures".

Noah Bell of Collider stated, "For Disney fans growing up in the 2000s, House of Mouse was like a dream brought to life.

Taking place primarily in a dinner club owned by Mickey, the show featured characters from virtually every Disney film made at that point interacting on a scale never seen before or since.

If hosting one of the biggest crossovers in television wasn't enough, the comical nature of the show provides a new angle to many iconic characters from older films, especially in its portrayal of some of the most notable villains over the years.