Gameplay of all versions of the game is similar to The Bigs and The Bigs 2. The game contains all the MLB teams along with the all-star teams and fictional Nicktoons teams in standard quick play games. For quick play games, 5 Nicktoons characters that have special abilities can be selected by each side. A few realistic baseball players from the chosen team also take part at bat and on the field. The game contains 6 fictional Nicktoons ballparks (7 in the 3DS version) and 6 real-life MLB ballparks (8 in the 3DS version) compared to the full MLB ballpark lineups in both The Bigs games.
There is also a tournament mode, where the player plays as any MLB team or a full team of Nicktoons characters to win a best-of-three-game series against other teams.
One of the game's other modes is called Distance Derby. This takes place in one of the fictional Nicktoons stadiums. The player selects an MLB player or Nicktoons character and tries to score points by hitting targets above the outfield. After one player scores 100,000 points, a turbo hit is activated for a game-winning hit.
Once the player beats a certain team or does something important in a game or Distance Derby, a card is unlocked. All of the player's cards are in a collection. If the achievement is done twice, the card will turn from Bronze to Silver. Doing so again will make it gold.