Set ten years after the events of Streets of Rage 3, the story features the playable characters fighting to free Wood Oak City from the control of the Y Twins, the children of previous series antagonist Mr. X.

Points earned goes towards a lifetime score, which goes towards unlocking bonus player characters from past games, presented in pseudo 16-bit style.

[2][3][4] The base game features five main playable characters; series veterans Axel Stone and Blaze Fielding; Adam Hunter, who originally appeared in the first Streets of Rage game and is unlocked through playing the story; and new characters Cherry Hunter, Adam's daughter, and Floyd Iraia, a part-cybernetic apprentice of Dr. Zan.

16-bit versions of characters from the original trilogy, including Max Thunder, Skate, Dr. Zan, and Shiva, can be unlocked by raising the lifetime score.

Ten years after Mr. X's death, Wood Oak City faces the rise of a new Syndicate, led by Mr. X's children, the twins Mr. and Ms. Y. Axel Stone and Blaze Fielding, along with Adam Hunter's daughter Cherry Hunter and Dr. Zan's apprentice, Floyd Iraia, fight the Syndicate around the streets until they are arrested under false accusations.

As they break out from their cell, they are approached by Mr. Y, who reveals that the police force is working for him and offers them a deal to join his side, but they refuse.

Following a hint to Chinatown, the heroes meet Shiva and learn from him that the Syndicate has a plan to control the entire city using a hypnotic signal they developed.

The heroes then stop a music show arranged by the Syndicate to spread their signal across the city and chase after their enemies to their main base in an island, where they fight and defeat the Y twins.

However, the game's programmer, Omar Cornut, had moved onto a personal project, so Fiquet and publisher Dotemu approached Sega about creating a full sequel to the series instead.

[8] The game's score was primarily composed by Olivier Deriviere, with additional compositions from Yuzo Koshiro, Motohiro Kawashima, Yoko Shimomura, Keiji Yamagishi, Harumi Fujita, XL Middleton, Scattle, Das Mörtal, and Groundislava.

[12] Hideki Naganuma was also originally set to contribute, but dropped out of the project due to scheduling conflicts before being replaced by Fujita.

The DLC adds three additional player characters who are also bosses in the game's main storyline; the current incarnations of Streets of Rage 2 characters Max Thunder and Shiva, and a newcomer Estel Aguirre, and a survival mode in which players fight through waves of enemies to unlock new moves and weapons, as well as the Streets of Rage 3 incarnation of Roo.

A free update adding additional color pallets, a training mode, and a "New Mania+" difficulty was released alongside the DLC, along with a version of the game for Google Stadia.

[28][29][30][31][32] Leo Faierman of The Sydney Morning Herald wrote that "the visuals, sounds and mechanics aren't as envelope-pushing in 2020 as the originals were in the early '90s, but the balance between embracing nostalgia and reformulating the brawler for the current decade is struck wonderfully".

[38] Michael Huber of Easy Allies stated that Streets of Rage 4 masterfully revitalized the series, describing the combat and soundtrack as high points, but criticized the online components at launch.