The game contains all the MLB teams along with the all-star teams and fictional Nicktoons teams in standard quick play games 5 Nicktoons characters that have special abilities can be selected by each side. Gameplay of all versions of the game is similar to The Bigs and The Bigs 2.
Both console versions allow the player to choose between traditional pad-based controls or motion controls, with the Wii version implementing the former with the Classic Controller and the Xbox 360 version implementing the latter with the Kinect sensor. The Nintendo 3DS version has two additional characters and more stadiums and modes. In addition to Nickelodeon characters, the game also features players from real Major League Baseball teams. Characters from Rugrats, Rocko's Modern Life, Aaahh!!! Real Monsters, Hey Arnold!, The Angry Beavers, CatDog, El Tigre: The Adventures of Manny Rivera, Back at the Barnyard, and The Mighty B! make cameo appearances in the game's loading screens. Puppy, and two characters that only appear in the 3DS version, one which is from The Adventures of Jimmy Neutron: Boy Genius, and the other from the Nickelodeon game Monkey Quest. It features playable characters from Nickelodeon shows including SpongeBob SquarePants, Invader Zim, The Ren & Stimpy Show, Danny Phantom, Planet Sheen, Avatar: The Last Airbender, Fanboy & Chum Chum, T.U.F.F.
The game was developed by High Voltage Software and published by 2K Play in 2011 as an indirect sequel to The Bigs 2. Nicktoons MLB is a baseball video game released for the Xbox 360, Wii, Nintendo DS, and Nintendo 3DS platforms.