MLB SlugFest 20-04 is the only appearance of Midway's arcade baseball series on the Game Boy Advance. Compared to the console version, it has a reduced number of gameplay modes and options and features traditional two-dimensional graphics.

Gameplay modes include Quick Play for a single exhibition match, Challenge (similar to a season, with one game against every team) and Series (best-of-7 World Series match). Progress in Challenge and Series modes is saved via passwords. The game includes licensed teams and players from the 2003 MLB season, along with six different ballparks.

Gameplay largely follows the traditional model: pitching and batting are seen from a view behind the batter, while the view switches to an isometric view of the field once the ball is away. The standard features of Midway's sports games can also be found here: players have a turbo meter that can be used to enhance their moves, and they can catch on fire after several successful plays, enhancing their abilities even further.