Dreams are doomed to die in Night City, a futuristic Californian metropolis. As a teenager living in the city's slums, David Martinez is trying to fulfill his mother's lifelong wish for him to reach the top of Arasaka, the world's leading security corporation. To this end, he attends the prestigious Arasaka Academy while his mother works tirelessly to keep their family afloat. When an incident with a street gang leaves David's life in tatters, he stumbles upon Sandevistan cyberware—a prosthetic that grants its wearer superhuman speed. Fueled by rage, David implants the device in his back, using it to exact revenge on one of his tormentors. This gets him expelled from the academy, shattering his hopes of ever making his mother proud. After witnessing David's newfound abilities, the beautiful data thief Lucyna Lucy Kushinada offers to team up with him, handing him a ticket to salvation. However, associating with Lucy introduces David to the world of Edgerunners—cyborg criminals who will break any law for money. Edgerunners often lose their lives, if the cyberware does not break their minds first; but in his fight for survival inside a corrupt system, David is ready to risk it all.

Eccentric and blunt, the walrus Hiroshi Odokawa lives a relatively normal life. He drives a taxi for a living, and there he meets several unique individuals: the jobless Taichi Kabasawa who is dead-set on going viral, the mysterious nurse Miho Shirakawa, the struggling comedic duo Homo Sapiens, and Dobu, a well-known delinquent. But Odokawa's simple way of life is about to be turned upside down. The case of a missing girl the police have been tracking leads back to him, and now both the yakuza and a duo of corrupt cops are on his tail.

Every five years, an exhilarating race called Redline is held, and the universe's most anticipated competition has only one rule: that there are none. Racers are pushed to their absolute limit—a feeling that daredevil driver JP knows all too well. Having just qualified to participate in Redline, he is eager to battle against the other highly skilled drivers, particularly the beautiful rising star and the only other human that qualified, Sonoshee McLaren. But this year's Redline may be far more dangerous than usual—it has been announced to take place on the planet Roboworld with its trigger-happy military and criminals who look to turn the race to their own advantage. However, the potential danger doesn't stop the racers; in fact, it only adds to the thrill. Relying solely on his vehicle's speed, JP prepares for the event to come, aiming to take first place in the biggest race of his life.

Daisuke Kanbe, a man of extraordinary wealth, is assigned to the Modern Crime Prevention Headquarters as a detective. It is there that he gets partnered with Haru Katou, a humane detective who values justice above all. The two are polar opposites, and their morals clash time and time again. Haru despises Daisuke for using monetary wealth to solve cases, as he believes that money isn't everything. The two will have to combine their efforts, however, to solve the mysteries that are coming their way.