The Warner Brothers and Sister first begin the game by telling the player "welcome to our videogame", before arguing on the absurdity of how they can be in a video game when they are cartoon characters, not video game characters. The main story is that the Warner Brothers and Sister are attempting to try to be closer to their favourite movie stars. Yakko forms a plan: they can open up a shop to sell movie memorabilia – so they must obtain four items from different movie sets to set it up.

The game features four main levels, which can be tackled in any order, in which the player must reach the end and beat the boss to obtain a piece of movie memorabilia. After clearing all four levels, players travel to the final level where they must fight Pinky and the Brain.

Players control Yakko, Wakko and Dot, switching control between them to use their respective powers accordingly. Yakko uses a paddleball to stun enemies, and is also able to push and pull objects such as crates. Wakko uses a mallet which can be used to hit switches, break certain objects and light fuses. Dot is able to blow kisses which, when used on certain characters, triggers certain actions needed to progress.

Like most video games, the Warner Brothers have health indicators and a number of lives. The lives can be increased by obtaining either 100 stars, or obtaining a small golden form of their faces. Their health is indicated by their faces on the top left of the screen. When they smile, they are healthy, but when they are looking either tired, unhappy, or weak, then they should find health soon (which is found in the forms of several forms of ice cream or sweets or other kinds of food). The levels are timed, so it is unwise to stay and wander aimlessly in one area.

This version was ported to the Game Boy by Factor 5, but due to space constraints, only three levels are present in this version and certain parts of the three levels are absent. Both the Science Fiction/Space Opera – Space Wars (Space Trucking) and nearly all of the final Action Movie - Once There Was A Man Named Oscar levels are absent from this version. On easy mode, the Game Boy version ends early and it ends on one of the three levels, making the game have a abrupt ending. On normal and hard mode, the Game Boy version continues after you beaten the first three levels and you go to Once There Was A Man Named Oscar and the final battle with Pinky and the Brain.

This game is out of the ordinary because movement is forwards, backwards, and side to side a movement style usually reserved for Beat 'em ups, in most side scrolling platform games the player can only go forward and backward. Pinky and the Brain once again have another plan to conquer the world by deciding to steal the script of the Greatest Movie ever while it was under development (this is not any actual movie or parody of one). The CEO of Warner Brothers studio reluctantly asks the Warner Brothers and Sister for their assistance to retrieve all 24 pages of the script, which is the primary objective of the game. This game can be completed without obtaining all of them, however. The game focuses more on parodies of films at the different stages that are once more based on different genres of movies.

This game is different from the Mega Drive/Genesis version. Firstly, the characters have no health bar, lives (the game ends when all the characters are defeated/captured, one by one) or special abilities making the game highly difficult due to the one-hit kills. Characters can pick up and throw things as well as execute a dash move. If all three are together, they can also stack themselves up to reach higher platforms. Secondly, there is the slot system, which is a slot machine at the bottom of the screen. It is activated after obtaining a certain number of coins and can be used for a range of power ups such as temporary invincibility or bringing back characters who were defeated or captured earlier.

Throughout the game, there are small robots with white block heads, red bodies and yellow appendages who work for Pinky and the Brain.

The Mega Drive/Genesis version received a 71% at Gamerankings. The SNES version received a 62% at Gamerankings. The Game Boy version received a 62% at Gamerankings.