When Smite launched its Nickelodeon crossover event, multiple characters were not voiced by their original voice actors.

• Invader Zim was voiced by Andrew Russell instead of Richard Horvitz
• Rocko was voiced by Matt Cowlrick instead of Carlos Alazraqui
• Jenny was voiced by Jenny Yokobori instead of Janice Kawaye
• Danny Phantom was voiced by Sean Chiplock instead of David Kaufman
• Powdered Toast Man was voiced by Michael Berger instead of David Kaye, his current voice actor and replacement for the now-deceased Gary Owens.

Zim's original voice actor Richard Steven Horvitz claimed that he was not allowed to reprise the role of Zim due to Hi-Rez Studios refusing to work with union actors, and that he felt insulted by the temporary recast. For Jenny, Rocko, and Zim, this game marked the first time they had been portrayed in English by someone other than their original actor.

When Danzaburou uses his Tanuki Trickery move with the Rocko skin from the Nickelodeon crossover event in Smite, a set of comics are spawned featuring Rocko's friends, each with a title that reads as "NAME the ADJECTIVE" - Filburt the Smart, Heffer the Slow, and Paula the Cook.

Dr. Paula Hutchinson is never referred to as simply "Paula" in Rocko's Modern Life, only "Dr. Hutchinson" or "Hutch", even after marrying Filburt Shellbach in "The Big Answer", and - although she takes on a variety of professions throughout the series - she is not a chef.

When Danzaburou uses his Tanuki Trickery move with the Rocko skin from the Nickelodeon crossover event in Smite, the lamp and its stand from Rocko's living room is summoned in the miniature set. However, the lampshade is modeled in a notably unfaithful manner to the source material, lacking its zig-zag splatter pattern and instead being blue all over, and going against the Rocko's Modern Life art style rules of making all inanimate objects slanted.

The Hindu goddess Kali's design was initially more revealing, however during the game's beta, her appearance was changed to have her more clothed, in addition to new voice lines and updated abilities.

It's thought that her redesign was due to receiving backlash from practicing Hindus, who also objected to her inclusion. However, it's also possible this was done due to working with Chinese publisher Tencent to make the game more family friendly.

The Egyptian god Khepri's victory screen shows him dancing, the animation seems to be based on a dance done by Jake the Dog in Adventure Time.

Ne Zha's dancing animation is a reference to the game Jet Set Radio Future, specifically Beat's dancing animation.

One of Ullr's emotes states, "I used to know an adventurer like you, until I shot an arrow in his knee", a reference to the popular line of dialogue in The Elder Scrolls V: Skyrim. Another references The Lord of The Rings by stating, "You have my sword, and my bow, and my Axe!"