According to producer Kensuke Tanabe around the game's release, Nintendo placed stricter guidelines on the Paper Mario series beginning with Paper Mario: Sticker Star. Tanabe previously mentioned these guidelines in a 2012 Iwata Asks interview for the latter game, stating it was originally a directive from series creator Shigeru Miyamoto. Under these rules, developer Intelligent Systems was no longer permitted to significantly visually modify existing Mario species through aspects such as age or gender, or introduce entirely new characters that expanded the broader Mario setting. As a result, they could no longer create distinctive versions of familiar species, such as uniquely-designed Toads, Goombas, or Bob-ombs with unusual body shapes and appearances, in the same style seen in the first two Paper Mario titles, although for Paper Mario: The Origami King, they were allowed to design different clothing and accessories for Toads. These restrictions also retroactively applied to older side characters and party members introduced before Sticker Star, prohibiting their return while the guidelines remained enforced (this presumably does not affect remakes as evidenced by the 2024 remake of Paper Mario: The Thousand-Year Door). Tanabe's 2020 comments on this restriction angered players who suspected that Nintendo had been exercising stricter creative control over the wider Mario series' character designs, a trend colloquially called the "Mario mandate", not helped by the hundreds of collectible, nearly-identical Toad NPC characters in The Origami King.

After getting the Blue Streamer, a Toad will appear at the entrance to the Shogun Studios, trying to look through a window and complaining about the price of admission, exclaiming "Let me in—LET ME IN!" This is likely a reference to the segment "Eric Near the DNC" from the Adult Swim series "The Eric Andre Show", which features a similar moment that became a popular internet meme.

A group of Toads surrounding a cactus in the Scorching Sandpaper Desert say the lines "Morbid stuff, huh?", "Free at last!" and "I need closure." when pulled from the ground. These lines are a reference to the 2019 album Morbid Stuff by Canadian punk band PUP, including the songs "Morbid Stuff", "Free at Last" and "Closure".

The game's sudden announcement two months before release was due to Nintendo's struggles in transitioning to a work-from-home structure during the COVID-19 pandemic.

If you inspect the steering wheel of The Princess Peach cruise ship while Bobby the Bo-omb is next to Mario, he will remark how he once dreamed of being a captain or an admiral. This is a reference to Admiral Bobbery, Mario's Bo-omb partner from Paper Mario: The Thousand-Year Door

The Sombrero Guy from Autumn Mountain may have been planned to be a temporary party member just like Spike and Bone Goomba, but was left out. Altering the code through save file hacking makes the character fully functional and adds an otherwise unused graphic to the pause menu.