Nawab, (Raghuvir Yadav) a popular novelist of Hyderabad, is suffering from the classic case of writer's block. Five years have elapsed. Stories of substance seem to have dried up. Almost providentially, Nawab comes across Meenaxi (Tabu). The young woman is enigmatic and individualistic. She's not quite willing to perform the part of a passive muse.

Meenaxi assumes different personae. She can be the mysterious perfume trader of Hyderabad, the exotic desert bloom of Jaisalmer and the orphaned Maria of Prague. Inexorably, she consolidates her command over the novelist. She dismisses his renewed attempts at writing as insubstantial and hackneyed, plunging him into a state of deeper despair. She is scathingly critical about his story and is amused by one of his characters, the lovelorn and awkward Kaameshwar (Kunnal Kapoor).

Nawab strives on a new page all over again. Meenaxi comments that perhaps the book is in vain. In any case, it is much too late. The writer must survive and live, if he can, without her support, inspiration and criticism. Delving into the limitless world of creative endeavor and vicissitudes in the way of such endeavors, Meenaxi: Tale of 3 Cities approaches myriad aspects, the relationship between art, the real and the imagined being just one of them.

The film, a collaboration between India's pre-eminent artist M. F. Husain and his painter son Owais Husain, while constructing a fictional story, leaves itself open to interpretations and readings by every viewer.