Two villains made their only appearance in this game, Chuck, a junkyard man with a tendency to vomit bizarre objects, and Doc Duodenum, a crazed organ of a giant alien. The game incorporates a large variety of villains in the boss battles, including Hickboy, Psy-Crow, Queen Slug-for-a-Butt, Evil the Cat, Bob the Killer Goldfish, Major Mucus and Professor Monkey-For-A-Head exclusive Robotic Chicken. Levels commonly culminate with a boss battle. Failure to do so results in Peter lashing out at Jim, taking away from his health. For example, the level 'For Pete's Sake', involves making sure the computer-controlled Peter Puppy character gets through the level unharmed, which is accomplished by whipping him to make him jump over pits, and defeating enemies before they can damage him. Some levels have additional requirements beyond merely getting to the end of the level. The whip move also allows the player to grab hold of, and swing from, certain hooks in the game. The player can use Jim's gun as a method of shooting enemies, or his worm body as a whip for whipping enemies. The player controls Jim and must maneuver him through the level while avoiding obstacles and enemies. The game plays as a 2D sidescrolling platformer with elements of a run and gun game as well. In 1991, Sega released the Mega CD or Sega CD, which was a CD-ROM add-on for the Genesis that allowed gamers to play CD based games as well as audio CDs.Jim in the 'New Junk City' level on the Super NES version The Genesis could do things that the NES simply couldn't. Sega also focused attention on its better graphics, speed, and sound, especially after the release of Sonic. Sega marketed the Genesis as hip, cool, and edgy. These efforts were often successful, Nintendo Exclusivity Clause not-withstanding.

In addition to porting over popular coin-op games, Sega executives worked hard to lure developers away from Nintendo. The Genesis was developed with the American market and consumer in mind. They are even available for download on the Nintendo Wii Virtual Console. Genesis games are re-released even today as part of collector's editions for the PS2, PSP, and other systems. Games continued to be released internationally as recently as 2002. It was the first successful 16-bit system, with a 14-year lifespan second only to the Nintendo Game Boy. It also inaugurated the Console Wars of the 1990s. Released in 1989, the Sega Mega Drive or Sega Genesis heralded the coming of the 16-bit era.

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