Radha is an accomplished playwright and teacher who is approaching her 40th birthday while grappling with the unfulfilled promise of a prestigious 30 Under 30 award she received nearly a decade earlier. Faced with stagnation in her career, her agent and friend, Archie, presents her latest play, Harlem Ave, to J. Whitman, a wealthy white producer. Whitman suggests that Radha’s work should delve deeper into Black suffering and offers her a writing position for a musical about Harriet Tubman, which angers her to the point of throttling him.
Struggling to find her voice in her career, Radha hears rap music booming outside her apartment, sparking inspiration to pursue her early passion for rap that she had buried since high school. In a bold move, she tracks down D, a music producer, and adopts the stage name RadhaMUSprime. However, Archie worries that this could signify a breakdown for her.
Though initially distant, D's attitude shifts after they collaborate to create a track together. To her surprise, he agrees to record a mixtape with her and invites Radha to showcase her talent at an event for emerging rappers. Yet, on the night of the showcase, her nerves get the best of her after she indulges in substances and forgets her lyrics, leading to an embarrassing moment in front of her students.
Meanwhile, Archie tries to mend her relationship with Whitman by leveraging the recent passing of Radha’s mother to persuade him to produce Harlem Ave. However, he insists on the addition of a white character to the play, which makes Radha feel increasingly uneasy about the artistic compromises she is forced to make to cater to a predominantly white audience.
Despite witnessing her disastrous performance, D remains a source of encouragement for Radha, urging her to persist with her rapping career. They attend an all-women's rap battle in the Bronx, which leads them to spend an intimate night together, sharing their experiences in the arts and coping with the loss of their mothers. Nevertheless, Radha pulls away from D the following morning, declaring her need to concentrate on her play instead.
As the production of her play advances, Radha contemplates her mother's journey as a struggling artist while clearing out her mother’s apartment with her brother. Much to her surprise, she finds that her brother views their mother as a talented Renaissance woman rather than a failure, providing her with renewed encouragement.
On the opening night of her play, Radha has a moment of clarity during the curtain call, where she boldly denounces her work and performs a rap calling for artists to remain true to their artistic integrity. In a dramatic turn, she fires Archie just as he resigns and rushes to D's apartment, where they are finally united. The film concludes with the duo walking together, as D beatboxes and Radha raps, transitioning from a striking black and white aesthetic into vibrant color, symbolizing her journey of self-discovery and creative liberation.
