Tom and Jerry Run is an endless runner based on the popular Tom and Jerry animated short films. Jerry, the mouse, needs the player's help to escape Tom, the cat, and collect as much cheese as possible. The runner-style carpets in the kitchen, hallways and other areas of their home serve as race tracks. Various types of cheese, including cheese wedges and wheels, float above different parts of the carpet runners.
Jerry starts running automatically. The player must direct him left or right through the floating pieces of cheese. They must also direct him to jump over and duck under obstacles, such as chairs and footrests. In some cases, a piece of furniture might have something stacked under it, which means the player must direct Jerry to jump over the object rather than slide under it.
If Jerry hits an obstacle, the run ends. The player must then start over and attempt to beat their last-best distance and number of collected cheese pieces.
Tom and Jerry Run offers a booster to help Jerry collect cheese. The player directs Jerry to run through a floating magnet. The booster then attracts the cheese to Jerry. It also offers the player a slow-motion tool.