The character might be the first Spider-Man villain to be in multiple active universes with no connection, played by separate actors.

SUMMARY

An theory on Reddit has pointed towards how the Chameleon could get his powers in the MCU.
The oldest Spider-Man villain, the character was closely associated with Nick Fury, who was actually the Skrull leader Talos in disguise.
The Chameleon is set to make an appearance in the upcoming film Kraven the Hunter and Your Friendly Neighborhood Spider-Man from Marvel Animation.

Spider-Man: Far From Home introduced audiences to Mysterio, one of Spider-Man’s most important and dastardly villains. Jake Gyllenhaal’s portrayal of the character had audiences believing that the character was genuinely heroic, even those who thought they knew how the character was in the comics. However, the film also introduced another important character into the MCU: Spider-Man’s very first antagonist from way back in The Amazing Spider-Man #1.

A still from Spider-Man: Far From Home/Marvel Studios
Dmitri Smerdyakov is the oldest antagonist that Spider-Man ever faced, better known as The Chameleon. Half-brother to Kraven the Hunter, the character has had a long history with Spider-Man, created by Stan Lee and Steve Ditko. Dmitri was present in Spider-Man: Far From Home as a background character, appearing in several shots as a close associate of Nick Fury (actually, the Skrull leader Talos in disguise).

A theory suggests that Dmitri Smerdyakov will appear in Spider-Man 4

Tom Holland as Spider-Man in Spider-Man: No Way Home / Marvel Studios
A theory on Reddit, brought forward by user u/ghostrider8303 suggested how Dmitri Smerdyakov could become the Chameleon, suggesting a slew of different routes that the MCU could take with the character to make him unique in this adaptation of the Marvel Universe. The theory suggests that Smerdyakov could be a Skrull himself, given that Talos could have surrounded himself with loyal Skrull while he posed as Nick Fury.

The theory also posits that if the character is indeed not a Skrull, he could get his hands on some Skrull DNA, or even employ the technology used by Mysterio to up his shapeshifting game. The theory does not talk about why an associate of Nick Fury would become a Spider-Man villain, but one can speculate how the character might become an antagonist for Peter.

To begin with, if the character is indeed a Skrull, then President Ritson’s mandate to treat all aliens as hostiles in the wake of Secret Invasion could have something to do with it. However, if the character is not a Skrull, the character could simply be a SHIELD agent sent to bring in Spider-Man, given that Peter is a fairly powerful superhero who has no public identity, or at least one that SHIELD would have a tough time deciphering. The character could make an appearance

The Chameleon is already set to make an appearance in a Marvel film

Aaron Taylor-Johnson in and as Kraven The Hunter/ Sony Pictures
Kraven the Hunter is also one of Spider-Man’s most well-known villains, making his latest appearance in Marvel’s Spider-Man 2 for the PS5. The Chameleon is the half-brother of Kraven the Hunter and is slated to make an appearance in Sony’s Kraven the Hunter,  which exists in its Universe of Spider-Man characters, starring Aaron Taylor-Johnson. The Chameleon will be played by Fred Hechinger of Vox Lux fame.

However, the character’s appearance in Sony’s Universe of Spider-Man Characters will serve as the first time a character has been shared by Sony and Marvel, actively appearing in the MCU and Sony’s own universe at the same time. While the Spider-Verse animated films do feature an alternate Peter Parker, it will be a first for Sony’s current live-action Universe, which is yet to deliver a different version of a character who has already appeared in the Marvel Cinematic Universe.

Apart from the film, the character is also set to appear in Your Friendly Neighbourhood Spider-Man, which is an animated property chronicling an alternate version of Peter Parker, one where he would be mentored by Norman Osborn as opposed to Tony Stark, as reported by Comicbook.com. This would be a third version of The Chameleon, concurrently existing in their distinct continuities in three active properties.