During development of the game, Peppino was stated to be a war veteran who suffers from post-traumatic stress disorder. Following the release of the game, this character trait would be retconned by the game's creator McPig, who suggested that he probably merely imagined his participation in conflict.

Two background characters featured in the Pizzascare level, a pink-clothed Peppino and a dark-skinned blue-clothed heterochromatic Noise, are fan characters known as Peddito and the Doise created by a fan named Robbie1scool. The Doise would be included as The Noise's exclusive boss in the Noise Update.

The game was originally planned to feature a "Heat Meter" that kept track of how many enemies the player was able to defeat in a row. More consecutive kills would build up the player's "heat," while getting hit and spending too much time without attacking enemies would lose heat. Higher heat levels would additionally make enemies more aggressive, increase the amount of points lost from taking damage, and grant Peppino new attacks. The development team compared this mechanic to a similar one found in God Hand.

The Heat Meter was fully implemented in a demo released to Patreon backers in April of 2021, but was simplified in later builds before ultimately being removed in October of 2022 due to mixed audience responses; several animations associated with it were also reconfigured for other purposes. Despite this, graphics for the Heat Meter and code for the more aggressive enemy behavior are still present in the final game. The Pizza Slug, Shrimp Thug, and Tribe Cheese enemies would also have their high-aggression modes enabled by default.

The title card for the "Gnome Forest" level became the subject of the "Lario" meme, which features an edited version of the card with the word "Lario" above the characters' heads as a mash-up of "Sneaky Snitch" by Kevin MacLeod and "Superstar" by Young Thug. This meme would go on to be referenced within Pizza Tower itself, with Gnome Forest's secret music being renamed "Everybody Wants To Be A Secret" after the meme became popular.

Pizza Tower first saw attention with the demo released in the fan-run Sonic Amateur Game Expo (SAGE) 2018. To coincide with the expo being themed around Sonic the Hedgehog, a temporary joke character named "Snick the Porcupine" was added, with a backstory detailing how Peppino (dressed in blue like Sonic) had intended to go to SAGE, but ended up at the "Snick Amateur Games Expo" and instead made do with Snick's games (Pizza Tower levels). Upon clearing the SAGE demo, Snick will then turn into "Snick.EXE", a parody of the Sonic.EXE creepypasta, starting an exclusive mode called "The Snick Challenge" where Peppino must evade Snick.EXE while playing through all 3 stages in the demo in order. The completion reward is a fully playable Snick with a unique moveset and animations, with taunts referencing a set of YouTube Poop music videos by user iteachvader that were based on the animated series Adventures of Sonic the Hedgehog.

Snick would later make a cameo in the SAGE 2020 demo for Antonball Deluxe - a game with connections to Pizza Tower - bringing back the same setting, playable Snick, and The Snick Challenge, but with Snick.EXE instead chasing the player through the regular demo playthrough and the requirement to collect "Ruckus Rubies" to unlock Snick. Since Snick was also not meant to appear in the final release, the Ruckus Rubies use directly-ripped sound effects from the Sonic series.

Despite his removal, Snick still makes many cameos in the final version of Pizza Tower. The tiles for the Slum hub area feature a Missing poster inquiring about Snick's whereabouts, the Refridgerator-Refridgerator-Freezerator stage features a similar Wanted poster on the side of a milk carton, one of Gustavo and Brick's taunts has Brick turn into Snick, and the Pizzaboy's Wash N' Clean area has Snick covered in a freshly-washed blanket, making him appear like a ghost. Peppino's blue outfit also returned under the name "Sage Blue", which can be unlocked by clearing Floor 1 in less than an hour.

If the player idles on the main menu for about 40 seconds without inputting anything, Peppino will eventually jumpscare them, causing the game to close itself.

In response to fans of Antonblast and Pizza Tower attempting to start an arbitrary rivalry between the two games, Antonblast creator Tony Grayson tweeted "Why not both?" with an illustration of Anton and Peppino deep kissing.