Uterine fibroids (UFs; leiomyoma) are the most common benign neoplastic threat to women worldwide, exacting an immense personal burden on female health and a monetary expense to the healthcare system estimated in the hundreds of billions of dollars every year globally. With no long-term non-invasive treatment option currently available to treat UFs, deeper insights regarding tumor etiology are the key for developing newer therapies. Accordingly, in this review, we discuss new mechanistic paradigm to explain UF tumor development through an exquisite model involving developmental reprogramming of myometrial stem cells due to early life endocrine disruptors exposure, inflammation, fibrosis, DNA damage, and eventually tissue stiffness. Further, we propose to utilize shear wave elastography as a potential screening tool for the early identification of women at risk for developing UFs who can benefit from several simple preventive strategies, including the consumption of natural compounds such as vitamin D and green tea as a safe fertility friendly non-hormonal modality to delay or even arrest or reverse UF progression.