In-game, nuclear waste is an opened, light gray barrel, filled with a bright, lime green solid with black dots speckled through it. The actual, green nuclear waste glows through surfaces of the map near the player. Nuclear waste is a fragile item - if the player crashes into an object with medium speed, the nuclear waste will detach from the vehicle, spin around, and explode in a green cloud and shock wave.
Nuclear waste appears only in Level 7, and only in four missions, each following the same general plot. The first time the player encounters nuclear waste is in Pocket Protector, when Professor Frink briefs Homer about the alien's weakness, which happens to be nuclear waste. After Homer realizes the power of nuclear waste, most of the missions that follow revolve around delivering nuclear waste. In Pocket Protector, and Alien "Auto"topsy Part I, Part II, and Part III, Homer delivers the waste, respectively, with Frink in the Hover Car, by himself in a car of the player's choice, with Snake in the Bandit, and finally with Grampa in his modified WWII Vehicle.
- In Alien "Auto"topsy Part I, Mr. Burns gives Homer a map of burial sites of nuclear waste. This map turns out to be pointless, as the nuclear waste is always found in the same place: the power plant.
- Nuclear waste is a health hazard to all life on Earth, and according to Frink, the Rigellians as well. However, the ability of the nuclear waste to destabilize and destroy an alien spacecraft would have to depend on the type of waste used, and whether the material used to create the spacecraft would malfunction in the event of contact with nuclear waste.
- Nuclear waste, vehicles and characters are all sacrificed to destroy the spacecraft, but no matter who is driving, Homer will always escape the tractor beam, even though, in canon, Frink, Snake, and Grampa are sent into the spacecraft, presumably to their deaths. How Homer can escape, but not these three is unknown.
- The first time the player disturbs the nuclear waste, a coin will come out the barrel, and the Hit & Run meter will increase. If the player crashes while relatively close to the power plant, the next barrels will not release a coin. Only when the player travels a moderate distance will the next barrel generate a coin.
- Because nuclear waste is deadly, even in tiny doses, the player can not collect nuclear waste on foot. The player can, however, stand on top of the waste and even kick it.