Mona Lisa was originally pitched as a female turtle by Fred Wolf Studios and Playmates Toys. At the time, both of the TMNT's co-creators, Peter Laird and Kevin Eastman, would turn this down as they thought it lacked creativity. However, Eastman would later reverse his stance and had a hand in introducing Ninja Turtles: The Next Mutation's Venus de Milo. Later prominent female turtles include IDW Publishing's Jennika and Lita.
1987 animated series
Mona Lisa was a college student on a fishing vessel that was attacked by a nefarious pirate named Captain Filch. In an attempt to sabotage Filch's nuclear reactor, she was mutated into an anthropomorphic lizard. She later met Raphael and teamed up with him to save a yacht of hostages from Filch. Despite apparently being Raph's love interest as of this episode, she was never seen again for the entirety of the series' run.
2012 animated series
Mona Lisa is the nickname given by Raphael to a Salamandrian (alien anthropomorphic salamander) named Y'Gthgba. She was mostly cold and militaristic, but Raphael warmed her heart. Unlike before, she had a handful of appearances and much screen time with Raphael.
Mona Lisa was finally introduced in comic capacity after IDW's Teenage Mutant Ninja Turtles #100, in which she is a mutant lizard victim of a mutagen bomb that was detonated in New York City by a mutant terrorist cat, Old Hob. She meets up with the aforementioned female turtle, Jennika, and fight off a trio of Hob's enforcers - Puggle the platypus, Bandit the raccoon, and Diamond the porcupine. Later, she meets Donatello, and being a physics major, she began developing a crush on the scientifically-inclined turtle.
Mona debuts at last as a video game character in 2020's Teenage Mutant Ninja Turtles: Mutant Madness. Her design is an altered version of her original 1987 series appearance.