The game is fairly similar to the first one albeit with a few changes. At its core it's an old school 2D platformer with a difficulty level to match. However, instead of 8 unrelated stages to choose from and a final stage, there are 5 different worlds with 4 stages each, and one final world with 2 stages. In order to play any stage in a world the previous stage in the same world needs to be destroyed.
The first stage is an introductory level where the Nerd will be able to acquire a new armor piece similar to the Mega Man X series. Every armor piece will grant the Nerd an extra ability, such as wall jumping, charge shot, more powerful shots, punching, the ability to see invisible blocks the Nerd can walk on, and floating in mid-air for a few seconds. Only the loafers are mandatory, which are acquired in the tutorial stage. These upgrades replace the different playable characters from the first game.
Every second stage ends with a mini-boss. In all worlds but two, the mini-boss is the Nostalgia Critic (parodying Proto Man from Mega Man 3), while the two exceptions are Board James and the Nerdy Turd. The Critic also serves as the first boss of the game, at the end of the tutorial level.
Secret NES cartridges are scattered across every stage except for boss stages and the Final Tower, spelling out N-E-R-D once they're all collected, reminiscent of the K-O-N-G letters from the Donkey Kong Country series. As long as the Nerd collected a cartridge and got to a checkpoint, or if he collected the cartridge and the player stops playing the level where he collected the cartridge, the cartridge is safe in his hands, otherwise it will return to its place when the Nerd dies.
- For a more in depth look a the enemies, and hazards in each stage, see "List of Angry Video Game Nerd Adventures 2: ASSimilation Hazards and Enemies"
Browntown is a sewer themed world (with elements based on TMNT NES; for example, it includes a 'jump' the player has to walk over). The Nerdy Turd appears in the 2nd level of this area as the mini boss. The main boss of this area are a parody mix between the Teenage Mutant Ninja Turtles & Battletoads and a rat who parodies Master Splinter. The first level of Browntwon is called "Dookie Dookie Panic", which is a reference to Doki Doki Panic, a Famicom Disc game that James and Mike played.
Based on James' Halloween-themed movie review marathon of the same name. The levels are mostly black and white until the Nerd finds a "Color Button" which adds platforms for you to complete impossible jumps and add color to the whole level. The boss of this world is a mixture of every monster cliche known as Sir Werepire who starts off as an expy of Dracula from the Castlevania series while referencing the opening scene from Castlevania: Symphony of the Night, but then turns into a werewolf who drags its itching butt across the battlefield, and suddenly turns into a giant werewolf knight. But it doesn't stop there, as the spirit of the monster comes back to haunt the Nerd who shoots it down. Then it comes back from the dead as a zombie, but the Nerd is so fed up with the fight being dragged out that he stops it right there and the monster goes back to its grave.
A board game themed level which also references episodes from James' series of the same name. Board James appears here as the mini boss of the 2nd level while Mr. Bucket appears here as the main boss of this area (though he is called Mr. Fuckit).
Based on the AVGN movie, while the name also is a reference to the Action 52 episode. The level has little relation to the movie, but does include the alien and various enemies such as E.T., The Military Robots, and Dark Onward. McButter also appears off screen when Dark Onward ordered her to fire Dick Missiles towards The Nerd.
Nerd Gaiden is a world that looks similar to Tokyo, Japan. It contains many enemies and signs that make references to anime, including "Balls of the North Star", which is a parody of the manga/anime series Fist of the North Star. There are even conveyor belts with plates of sushi and a giant flaming tanuki named "J Li Tanuki" who has giant testicles hanging out to do battle with his rival Scrotoro, which also parodies the titular character Totoro from the anime film My Neighbor Totoro. Only then does the Nerd meet up with a mixture of Hello Kitty and the ED-209 from Robocop called CAT-209. If the player succeeds in killing CAT-209, he'll say "Fuck you nerd" in binary. The name of this area also is a reference to the Ninja Gaiden episode. The first level of Nerd Gaiden is called "Hang Dong '97", which is a reference to Hong Kong 97, a Super Famicom game that The Nerd reviewed in 2015. The background music even has a sped-up version of "I love Beijing Tiananmen," A.K.A. "I Love Peking Tiananmen", the 5-second loop that played infinitely in Hong Kong 97. The name "Nerd Gaiden" is a reference to "Ninja Gaiden"
A recreation of the final level from AVGN Adventures 1. The Nerd is inside the Virtual Boy and must climb the tower to stop the Nostalgia Critic from getting the glory of destroying Death Mwauthzyx and saving the world. The first level in this area is a reference to the Virtual Boy episode.