Madden NFL 06 is the second contribution by developer Exient to the series on the Game Boy Advance. It is based closely on the previous year's version, with the same graphics engine, similar menus and all previous game modes included. It adds updated rosters for the new season and one new game mode.

Exhibition games and full seasons, practice mode, situation mode, Two Minute Drill and the Madden Challenges for collecting Madden Cards are all the same as in last year's game. The new mode is called Mini Camp and consists of a number of mini games that can be played for high scores. They include goal kicking, passing, running and tackling.

Most modes can be played by two players over the link cable.