The first film in the series to not be directed by Genndy Tartakovsky.

The first Hotel Transylvania film to have a co-director.

The first Hotel Transylvania film in the franchise not to feature Kevin James as Frankenstein. Instead, Frankenstein is voiced by Brad Abrell.

The first Hotel Transylvania film in the franchise not to feature Adam Sandler as Dracula. Instead, Dracula is voiced by Brian Hull who also voiced the character in Monster Pets: A Hotel Transylvania Short Film (2021).

Steve Carell was considered to replace Adam Sandler as the voice of Dracula before Brian Hull was confirmed.

Jim Gaffigan's second animated film of 2021, after Luca (2021).

Jim Carrey was considered to replace Kevin James as the voice of Frank before Brad Abrell was confirmed.

Sony Pictures Animation's first and Columbia Pictures's second Amazon Studios exclusive film.

The first Hotel Transylvania film to be released by a different distributor other than Sony Pictures Releasing, since the rights were sold to Amazon Studios in August 2021.

The first Hotel Transylvania sequel not to be released the same year as a Goosebumps movie. Hotel Transylvania 2 (2015) was released the same year Goosebumps (2015) was released. Hotel Transylvania 3: Summer Vacation (2018) was also released the same year Goosebumps 2: Haunted Halloween (2018) was released.

Hotel Transylvania: Transformania will release on the 10 years after the original Hotel Transylvania (2012).

Was planned to be released in July, which would have made this the second Hotel Transylvania movie released on that month, after Hotel Transylvania 3: Summer Vacation (2018), but was pushed to October. This now marks this the third Hotel Transylvania film released in an autumn month.

Not counting the direct-to-video sequels of Open Season (2006) and Surf's Up (2007), as well as Smurfs: The Lost Village (2017), this marks the fifth time in a theatrically released animated film from Sony Pictures Animation where characters had been recast, in this case with Dracula, Frankenstein, and Tinkles, the first was Cloudy with a Chance of Meatballs 2 (2013) with Earl Devereaux, Hotel Transylvania 2 (2015) with Murray the Mummy, Hotel Transylvania 3: Summer Vacation (2018) with Blobby, and The Angry Birds Movie 2 (2019) with Terrence, Jay, and Brad.

This movie was shown alongside the new CG animated short film Nina (2022) from Sony Pictures Animation's ShineShorts in select theaters.

The first film to have the Destination Animation logo.

Was scheduled to be released in October, but got pushed to January 2022, which makes this the first Hotel Transylvania film released on that month. It's also the first film released 4 years apart, as the first two sequels were released 3 years apart.

The fourth theatrically released animated quadriquel after Shrek Forever After (2010), Ice Age: Continental Drift (2012), and Toy Story 4 (2019).

This is the second film celebrates Sony Pictures Animation's 20th Anniversary, after The Emoji Movie 2 (2021).