Queens on the Run follows four women, Mia, Tanya, Sarah, and Cassie, who reunite for a road trip after ten years of graduating high school. As they hit the road, they face the challenges of adult life and the memories that come with revisiting their hometown.
Along the way, they deal with car problems, run-ins with ex-boyfriends, and unexpected detours. However, they soon realize that the biggest obstacle they face is their own personal struggles and differences. Mia is struggling with the decision to leave her job and pursue her passion for music, Tanya is dealing with a recent divorce and the challenge of being a single mom, Sarah is facing infertility and a strained marriage, and Cassie is hiding a secret about her health.
As they work through their issues and support each other, they also encounter quirky characters like a hitchhiking clown and a group of rebellious teenage girls. Through these interactions, the four friends learn valuable lessons about the importance of friendship, taking risks, and embracing change.
In the end, they arrive at their destination, the iconic music festival Coachella, where they experience a transformational journey that solidifies their bond and friendship.