According to Ayano Koshiro, Adam did not turn for the sequel because he didn't have a special play style compared to Axel and Blaze.

"You had Axel, your standard fighter, then Blaze, the speedy character. But there was also Adam in the first game…. but Adam had no real speciality… (laughs) So he was out. (laughs)"

According to Ayano Koshiro, all the visuals for the characters and their moves were inspired by having played Street Fighter II with her brother, Yuzo.

"I’m sure you’ve played Street Fighter II—my brother and I did too. We liked it so much we bought a cabinet and had it installed in the office at Ancient. My brother and I liked the way they fought in SFII, and between the two of us, a shared vision of the fighting of Streets of Rage 2 arose: two jabs, followed by a straight punch, then some heavy hit, and the enemy goes flying! That kind of flow had to be in there."

According to the game's composer Yuzo Koshiro on his Twitter account, he found an internal document for "Stage 7: Munitions Plant" from Streets of Rage 2 that revealed the stage used ideas from the manga series Akira, and particularly influenced the second half of the level which takes place on an elevator.

In the Marukatsu Megadrive interview, the game's composer Yuzo Koshiro was asked about what music influenced the game. He responded: "I started writing the music last Spring, which was right around the time The Orb was coming to Japan, and everyone (myself included) was super excited about that. I was listening to Prodigy and Eon too, stuff with weird lyrics."

Ayano Koshiro stated that she and her team love reading various of "Weekly Shounen Champion" manga, mainly "Baki" and "Apocalypse Zero" manga series. They were a big influence to the game and there were lots of mangas referenced in the game.

In the European version the main title has the same "Streets of Rage" title image used in the US version, but uses the roman numeral "II" similar to the Japanese title. The American release simply uses the number "2".

In the Japanese release "duel" mode is listed as "battling" in the main menu.

In the Japanese version Mr. X is seen smoking a cigar in the last level. This was censored in international releases.

In the Japanese version of the game, "Bare Knuckle 2", Eddie "Skate" Hunter is named Sammy.

In the US version, Blaze's flying kick pose was altered to censor her underwear.

Sound test track 10 on the ##Sega## Master System was intended to be the battle theme for Mr. X. But since there aren't any changes with the music in the area, Shiva's theme will be heard when they are about to fight.