Though it is based on the movie in terms of plot and additional dialogue, the game was different from the movie. The NES port uses sound effects from the early 1990s The Simpsons games such as Bart vs. the Space Mutants.

Certain changes made the game more interesting in an interactive game than in a static movie, such as use of different weapons and power-ups for protection, level layouts with enemies not seen in the movie, and for the Uncle's House level, usage of hidden keys and locked doors gained only after luring Marv or Harry into specific traps laid out in the various rooms (aka the first two Home Alone movies), as well as an active scene involving the Bird Woman and her birdseed attacks.

The Nintendo versions of the game were released in late 1992 for all three Nintendo's consoles at the time. The Nintendo consoles are virtually the same game, with minor differences with each version. Stages two and three are all different in each version. For example, Stage 3's basement floor is only one screen in the NES version, a whole floor in the GB and SNES version. However, the Game Boy version has bottomless pits everywhere that Kevin loses a life if he falls in. All three games were published by THQ and developed by Imagineering. All three games have the same weapons: a dart gun to stun enemies, a necklace that can be flung to hit enemies on the ground, and two types of rocket-propelled fist launchers: a shorter version that can hit stronger enemies and a long-ranged version.

The Super NES version, while boasting a soundtrack with the Super NES traditionally realistic sounding instrument synth, suffered due to slightly post-8-bit graphics and sound effects, as well as a disjointed feel of incontinuity between stages. Kevin cannot recover his energy with cookies not being in this version.

The NES version has four different levels, the first of which is the Plaza Hotel. Kevin races through various floors and rooms collecting power-ups and avoiding the hotel staff, crazy guests and runaway vacuum cleaners and suitcases. Before he can escape, however, he has to deal with two bosses: the ever-persistent House Detective and the Master Chef. The next level takes place in Central Park, and is similar to the Plaza Hotel: Kevin collects his goodies while avoiding rats, bats and assorted thugs.

The third level takes place in Kevin's uncle's three-story Townhouse. This time Kevin has to avoid Harry and Marv, and sets up several booby-traps to keep the bandits at bay. While doing so, Kevin must also find keys that will allow him to escape to the next floor, and ultimately the Rooftop. Once he's on the roof, Kevin escapes to the streets of New York with the Bandits hot on his tail, until he reaches the giant Rockefeller Center Christmas Tree. It is here where he gets help from the Pigeon Lady to defeat Harry and Marv, have them sent back to jail, and finally reunite with his family.

The Game Boy version is virtually identical to the NES version, with a couple enemies and parts of the game exclusive to this version. Kevin has only four hit points instead of five like in the SNES and NES versions. The second stage has him running into hippos, monkeys that throw banana peels at him and a panda that juggles balls that will hurt Kevin if he comes into contact with. The third stage, as mentioned, has bottomless pits that will cost Kevin a life if he falls in. The final level has Kevin running away from: rats, dogs, trashcan lids and a safe that crushes him if he stays on the screen too long.

The MS-DOS version has been released in 1992. It has fourteen levels and stills of the movie after you finish a level. It starts with Kevin McCallister once again alone, but this time lost in New York. The Wet Bandits (Sticky Bandits) chase you through the streets of New York. You can use objects like garbage can lids or mustard bottles, necklaces, bananas, lettece to throw or drop to keep the Wet Bandits from catching you. Then you go to the Plaza Hotel and the Wet Bandits are still after you. You finish and you're back in the streets of New York. Harry and Marv will then chase you into Duncans Toy Chest. You can use toys to stop them. Then You lead them to your Uncle Rob's BrownStone. You can use your booby traps to stop them this time. Then after running through floors of the BrownStone. You get to the roof and try to get to the ladder. You get to the last level and get chased through the streets of New York again. You get through that level and get to the Rockfeller center Christmas tree to meet your mom, Kate, and win the game.

The Sega Genesis version was released a year later in 1993. It has eight different levels and starts Kevin out at the Airport, in which he must make his way to the elevator while avoiding airport passengers, airport security, and Harry who awaits his arrival at the elevator in which Kevin must defeat him using baseballs, a slingshot, or a bazooka shooting sticky balls of unknown material. In the second level Kevin finds himself in "the land of the lost luggage" where he must find his mother's red handbag while avoiding runaway luggage, workers throwing luggage, and of course the wet bandits aka: the sticky bandits. The third level involves Kevin trying to make his way across town to Duncan's Toy Chest avoiding falling Icicles, falling water, cats, people passing by, and the Bandits.

In the fourth level Kevin must navigate his way through Duncan's Toy Chest staying clear of the numerous different toys that will try to hurt him, and Marv and Harry. In the fifth level Kevin must once again make his way across town to get to his uncle and aunt's house all the while battling thugs, men throwing bottles from a window, cats, rats, birds, and the wet bandits along the way. It is at this point the wet bandits now possess new attacks such as Marv's jumping leap attack and Harry can now toss a bag of unknown contents at Kevin making the game more challenging. In the sixth level Kevin has to travel through a pipe leading to his aunt and uncle's house and with a flyswatter handy he fights his way to the end swatting hornets and bubbles.

In the seventh level Kevin is now in his aunt and uncle's house and must browse through the house avoiding rats and the bandits. Then Kevin comes to the eighth and final level in which he is now in central park and avoiding thugs, birds, falling snow, cats, and the wet bandits who are now desperately trying everything in their power to stop Kevin from jumping up the snow platforms in order to reach the Bird Lady at the top who saves Kevin and defeats Marv and Harry. The game ends with Kevin and his mother reconciling next to the Rockefeller Center Christmas Tree.

The game has had very poor reception. Most reviewers complain that various elements of the game change depending on what part of a level the player is on; for example, the slide attack is an effective move on one part of the level, but does not work on another.

Home Alone 2: Lost in New York was awarded Worst Sequel of 1992 by Electronic Gaming Monthly. They also awarded it Worst Movie-to-Game of 1996.