There are two attacks in the game that reference games developed by Ludosity, the studio who developed the first Nickelodeon All-Star Brawl game and also provided support on the second game. The Angry Beavers' jab attack is named after the platform fighting game Slap City, while Invader Zim's airborne back light attack is named after a Flash game developed in the company's early years called Garden Gnome Carnage.

In the weeks prior to Nickelodeon All-Star Brawl 2's release, a near-complete prototype build of the game leaked online. The Twitter account for the game's main developer, Fair Play Labs, accidentally retweeted a GIF of SpongeBob dancing from an unrevealed sound test mode and promptly deleted it. Community manager Thaddeus Crews expressed that, while he didn't have a particular moral problem with fans playing the leaked build, he advised against competitive players using it for practice due to how outdated it is.

Squidward's forward tilt in Nickelodeon All-Star Brawl 2 is based on a meme that went viral around the first game's pre-launch, showing a screenshot of Squidward kicking with poorly aligned fighting game hitboxes and the caption "AH HELL NAW SKODWERD GOT THE JANKY ASS HITBOX". Despite this origin, the move's hitbox "isn't very janky".

Despite many of the more unusual character picks in the first Nickelodeon All-Star Brawl being noted as characters the development team had to push Nickelodeon into allowing them to use, Grandma Gertie in Nickelodeon All-Star Brawl 2 was actually pitched by Nickelodeon corporate, something community manager Thaddeus Crews has stated to be akin to "selling blood to a vampire".

Originally, Donatello's Super Move was intended to be slightly different. Instead of driving the Turtle Van and shooting lasers at opponents with the other 3 Turtles, he would've perched atop the van alone, remote in hand, and rammed opponents directly.

In the Switch version of Nickelodeon All-Star Brawl 2, there exists a glitch where Rocko's winning animation will show a giant black texture in an unfortunate spot, resembling a vertical censor bar. This has a coincidental resemblance to a running gag from Rocko's Modern Life, where a horizontal censor bar will cover up Rocko's bottom half whenever he is shirtless, despite him usually being able to go pantsless without issue, being a cartoon animal. This has yet to be patched.

Nickelodeon All-Star Brawl 2 has been noted as having almost zero similarities to the game it is a sequel to from a gameplay perspective. Gameplay and moveset designer and community manager Thaddeus Crews would address this disparity in a short Twitter thread shortly after the sequel's launch by reassuring fans who prefer the first NASB that the sequel was not intended as a replacement for the first game: