The film begins with two New York street criminals Tommy (DMX) and Sincere (Nas), along with their associates in crime Mark and Black. The four violently rob a nightclub, murdering multiple patrons and what is assumed to be the nightclub owner. Once escaping, Black goes home while the rest retreat to Tommy’s house. While watching television, they are interrupted by Tommy’s girlfriend Keisha (Taral Hicks), who was awakened by the noise the group of men are making. Seeing it is time to depart, Sincere soon leaves and is followed in gesture by the others. He returns home to his girlfriend Tionne (Tionne “T-Boz” Watkins) and infant daughter Kenya. Meanwhile, Tommy is informed of a new form of heroin which he takes as a lucrative business opportunity.
Tommy subsequently meets with Sincere to discuss the venture. His rhetoric is met with resistance from Sincere, who has become enlightened to the plight of urban poor. After Tommy ridicules Sincere for his sentiments and mentions his connection with a Jamaican drug lord “Ox” residing in New York City, Sincere reluctantly agrees. Tommy then visits Ox in his particularly lavish mansion, to plead for Ox’s assistance in obtaining the heroin. Ox agrees on the grounds that Tommy and his men perform exceptionally in returning the money he invests in them.
At Mark’s grandmother’s basement, the group convenes to discuss the imminent flux of business. The narrator explains that one of Tommy’s associates, known simply as “Knowledge”, is to be involved in the operation. Meanwhile, Sincere confronts Black concerning the division of the money from the robbery the night before. Black believes he should receive as much of the share as Sincere, and when he continues to express his thoughts with a few minor insults, Tommy becomes incredibly enraged. He pushes Black to the floor and forces him to strip naked in front of everyone while firing a handgun wildly into the floor. Tommy then orders Black to sit on the couch, as he visibly harbors hostile feelings towards the rest of the men.
The duo, along with some of their friends from the neighborhood, including Knowledge and Mark, start transporting drugs (hidden in their car bumpers) from Queens to Omaha, and begin to overrun the drug business there. This is met with jealousy from a local drug dealer named Big Head Rico (Tyrin Turner), who informs the police of their activities. This results in a raid at their stash-house, which quickly results in a shootout between Mark and police officers. In a subsequent car chase, Mark loses consciousness and presumably dies while Knowledge is arrested. Knowledge calls back home from the local jail and is told by Keisha that Tommy isn’t there, nor should he have called home since the FBI had placed wire taps on their phone. Knowledge gets angry that Tommy won’t come to bail him out, and calls up Shameek aka Father Sha (Method Man), to not only infiltrate Rico’s gang, but to handle Tommy. While at a strip club in Omaha, Shameek confronts Rico and informs him that Knowledge sent him here to kill him and his associates. When Rico tries to run from Shameek, Shameek shoots and kills Rico as well as some members of his crew. While reloading his guns, the bartender shoots Shameek with a shotgun out the club and he manages to escape from the cops with injury.
Meanwhile, Tommy goes to Jamaica with Ox, and kills Sosa, the son of a drug lord there, at a stoplight while dressed as a homeless man, as a favor to Ox. Meanwhile back in Tommy’s house, Keisha is arrested by police and later bailed out by Tionne, with Tommy finding about the raid and quickly escapes. Later when the deceased’s family and friends finds out that is was Ox who ordered the hit, Pelpa, the gang’s leader and close friend of Sosa, sends a hit squad to kill him in his home, and Ox is able to kill them all before a femme fatale named Chiquita swoops down from his top floor and slits his throat.
On a parallel timeline, Tommy is cheating on Keisha with 17 year old Kionna. After both women shared words with each other (where Kionna taunts Keisha with Tommy’s infidelities), it becomes clear that Tommy is not willing to give either of them up and hooks up with Kionna secretly while living with Keisha.
While this is going on, Sincere has been trying to get out of the drug game and move his girlfriend and child to Africa, despite Tommy’s jokes that he was getting soft for wanting to leave. They make plans to leave on New Years, 2000. However, now Sincere is suspicious of Tommy; since the Omaha incident, Tommy has been on the run and was caught in Atlanta, GA, along with two young dealers from the neighborhood, Wise and LaKid, selling marijuana. One night at dinner, Tommy instigates an argument between Wise and LaKid, in which causes both men to draw out their guns and LaKid shoots Wise dead. Tommy, who is extremely intoxicated and is under heightened euphoria and relaxation from the effects of marijuana, remains seated, calmly glancing at Wise’s dead body as the police arrive to arrest him and soon, he is later released. Sincere feels that Tommy would give him up to save himself. This was not the case. Tommy was chosen by federal agents to assassinate a black Muslim leader, Rev. Saviour, (Dr. Benjamin Chavis) who had been preaching against the government on New Year’s Eve.
Later on, Sincere talks with his pre-teen friend, Shorty about what is going on lately and getting out the drug dealing, this is reminiscent of the third verse in the Nas song “One Love”; where he describes conversing with a 12 year old caught up in drugs and violence, Nas parts from the kid giving him a chain as a gift. Tionne later comes home from shopping only to find Shameek and a few other men waiting for her inside and when he asks for Sincere and Tommy, Tionne draws out her gun while they draw out theirs, but decide to spare her life and leave. Later while talking to a friend (AZ) outside a barbershop, Black and an accomplice confront Sincere and shoots him in the leg, which causes Sincere to shoot both Black and his accomplice dead and takes off.
On New Years’ Eve, Tommy confronts the leader in his study before he was to make a massive speech of hope and points his gun at him. The leader convinces Tommy not to go through with his mission, even though it was betraying the government and now putting his life at risk.
At the same time, Shameek visits Keisha’s home, in the hopes of finding Tommy there. Shameek slaps Keisha around, but Keisha is able to grab his gun right before he was going to kill her, turning the gun on him instead of her.
Sincere, having known everything that was going on, and surviving an attempt on his life too by his old friend Black, takes that moment to get out of New York as his family starts life over in Africa.