The game takes place in a post-cyberpocalyptic New York called "Neo New York", after a "chaos dunk" causes the death of millions. Twelve years prior to the game, Charles Barkley, in an attempt to impress his son Hoopz Barkley, performs a Chaos Dunk -- and inadvertently kills almost everyone present. As a result, basketball was made illegal and nearly all great players were killed in "The Great B-Ball Purge of 2041" (a.k.a "B-Ballnacht"). In 2053, another Chaos Dunk rocks Manhattan, killing fifteen million, and the blame falls on Charles, who is believed to be the only human capable of performing the Chaos Dunk. With the help of the Ultimate Hellbane, Charles escapes his pursuers: the B-Ball Removal Department, led by ex-NBA all-star Michael Jordan. Charles follows Ultimate Hellbane through the B-Ball Catacombs to the tomb of LeBron James, discovering that the Ultimate Hellbane is actually Balthios - the Octoroon great grandson of LeBron James. James contacts Charles from the B-ball dimension, offering him a warning which tells him to "seek the Cyberdwarf." After James vanishes into the b-ball dimension, Charles and Balthios enter the sewers under Neo New York to find the Cyberdwarf. Shortly after entering, they encounter a cyborg -- who they discover is Vince Carter. Carter, now named Vinceborg 2050, reveals that -- after he was killed in the Purge, someone had rebuilt him. However, he cannot remember who did it or why, and joins Charles and Balthios hoping to recover this memory. The three find Cyberdwarf in a town called Cesspool X, who assumes that Balthios brought him the wrong Barkley -- he wanted Hoopz. Cyberdwarf joins them and they rush to the church, where Balthios took Hoopz before rescuing Charles. Upon reaching the Church, they find that Jordan had arrived before them, killed the priest Larry Bird, and is holding Hoopz hostage. When Hoopz approaches the altar of the post-cyberpocalyptic version of God, Clispaeth, Cyberdwarf notes that Hoopz might be "The One." This triggers the return of Vinceborg's memory, and he explains that he was created by the terrorist organization B.L.O.O.D.M.O.S.E.S. to kill him. Charles, Balthios, and Cyberdwarf try to stop Vinceborg, with Jordan joining with him. Vinceborg and Jordan retreat after being defeated, and Charles, Hoopz, Balthios, and Cyberdwarf return to Cesspool X. When they arrive, Cyberdwarf suggests that B.L.O.O.D.M.O.S.E.S. has likely used the "Ultimate B-Ball" (allegedly the basketball used in the film Space Jam to absorb the balling skills of five NBA stars, of which Charles Barkley was one) to perform the Chaos Dunk, so they visit the old Spalding Building in Proto Neo New York -- where it is rumored that an extremely powerful basketball was being created before the Purge. The party reaches the sewer ladder leading to Proto Neo New York, but find that Dr. Allard -- a cosmetic surgeon profitting off of Cesspool X's citizens -- has a guard posted at the ladder, demanding a fee of five thousand neo shekels (the currency of the game) for passage into Proto Neo New York. Charles refuses the toll and defeats Dr. Allard in combat, and so the party finally reaches Proto Neo New York. While resting, Charles tells Hoopz about Clispaeth -- who was crucified two thousand years earlier in an event called the "Boston Massacre", which led to a massive rebellion called the Cyberpocalypse. The discussion is soon interrupted by diabolic laughter; the party rushes into what remains of a large building, where ex-WNBA player Juwanna Mann has sought shelter. She explains that Proto Neo New York's present state is the fault of the "Ghost Dad", preventing travel to the Spalding building. Charles has no choice but to defeat the Ghost Dad and lift its curse. After defeating the Ghost Dad, the party finally reaches the Spalding Building, where they must find two keys to activate an elevator. While searching for the keys, they discover fragments of information regarding the "Hell B-ball" that Spalding was creating. In the process, they learn that Spalding was using highly volatile "slamicite" in the ball, and that Dr. Cosby -- one of the scientists working on the ball -- was concerned about the ethics of creating such a powerful basketball. In a series of flashbacks, it is revealed that even after a test subject performed a mini-chaos dunk using the ball, development continued with the addition of more slamicite. Dr. Cosby later decided to leave the project; however, as he was leaving, a janitor picked up the prototype Hell B-ball to give it to Dr. Cosby, and inadvertently performed another chaos dunk -- killing everyone present and turning Dr. Cosby into the Ghost Dad. When the party finally retrieves the keys and proceeds through the elevator, they encounter Scott Creelman - who fights Charles to test him, and to make sure that he is worthy of wielding the Hell B-ball. After his defeat, he gives Charles the prototype Hell B-ball, explaining that it needs to be recharged with "manufacted jamicite". Before the party can leave, Hoopz collapses suddenly after being shot by a dart. Jordan appears to explain that the dart contained Type 2 Diabetes -- "the type they were never able to cure". He then leaves as quickly as he appeared, explaining that Hoopz will die very soon. The party travels to Liberty Island, where the rumored "Yelmirb" being can cure Hoopz's diabetes. After defeating Reginald -- ex-member of the "diabetes cult" that worships Yelmirb -- the party acquires the keys to the Statue of Liberty, where they expect to find Yelmirb. However, before they can enter, a sugar-based monster called the "Diabeastie" attacks. After defeating the monster and entering the tower, they discover that Yelmirb is actually Wilford Brimley -- and that he has the ability to "take a person's diabetes and make it his own." He is attached to a massive insulin machine that keeps him alive, but unfortunately, he can only cure one more person before he dies. Charles convinces him to cure Hoopz and places him into the machine. While Hoopz is in the machine, Vinceborg returns, attempting to kill Hoopz once more.
By the time the party defeats Vinceborg, Hoopz is cured, and as Wilford Brimley dies, the party leaves to travel to the outskirts of Neo New York -- the location of Cuchulainn's Tomb and the manufacted jamicite. Inside the tomb, the party is forced to split up to activate four switches. Cyberdwarf warns them that Cuchulainn will show each of them the thing they desire most, and if they touch it, Cuchulainn will be freed from his tomb. Each party member, except for Hoopz, encounters Cuchulainn's illusion, and both Cyberdwarf and Balthios avoid touching the objects. Charles, however, fails to resist the illusion and frees Cuchulainn. After opening the gate, the party regroups and approaches the Jamicite. Charles recharges the Hell B-ball -- and through it, feels another basketball calling out to him. While the others wait outside, Charles journeys farther into the tomb and discovers the first basketball, Shimmerglobe. Shimmerglobe teaches Charles a technique called "Double Dribble", allowing him to use both the Hell B-Ball and Shimmerglobe simultaneously. With both basketballs in his possession, Charles leaves the tomb and returns to the group, having everything they need to confront B.L.O.O.D.M.O.S.E.S. Charles uses the power of the Hell B-Ball and locates B.L.O.O.D.M.O.S.E.S. on the slave ship, Necron 5. Using Cyberdwarf's repaired spaceship, they travel to the Necron 5. When aboard, they encounter Vinceborg once again; however, Charles manages to restore his memories of who he once was, and Vinceborg resists his programming long enough to self-destruct. Deeper inside, the party encounters an old basketball court, and Michael Jordan appears to challenge Charles to one final game. They defeat Michael Jordan and finally reach the center of the Necron 5, finding the leader of B.L.O.O.D.M.O.S.E.S. -- who reveals himself to be Shadow Barkley: a copy of Charles created by the Ultimate B-Ball. He plans to use the Ultimate B-Ball to destroy all life on earth and use Charles's clones to begin a new era of basketball. When he is defeated, he laughs and explains that even if he dies, the machinery on the Necron 5 will trigger the Chaos Dunk and destroy the human race. Charles tells Cyberdwarf and Balthios to take Hoopz to the escape pods and leave. On the way, Balthios stops to hold off the Monstars and allow Cyberdwarf and Hoopz to escape. With Hoopz safe, Charles tells Shadow Charles that "there's only enough time for one last dunk," and performs a Chaos Dunk -- destroying Shadow Charles, the Necron 5, the Ultimate B-ball, and possibly himself and Balthios. The ending shows Cyberdwarf and Hoopz looking out the pod window. Hoopz asks the Cyberdwarf where they're going to go.The Cyberdwarf says he does not know, possibly a new planet.