Ovarian cancers constitute a poor prognosis disease. Due to their absence of symptoms, ovarian cancers are generally diagnosed at late stages. Despite major breakthrough regarding ovarian cancer surgery, minimal residual disease-induced relapse is still a hurdle for clinicians.Tumor microenvironment is a key actor on disease progression and resistance to therapy. In this study, we have focused on two major components of the tumor stroma, on one hand, the mesenchymal stem cells, and the endothelial cells on the other hand.We were able to demonstrate that mesenchymal stem cells are critically involved in ovarian cancer progression and resistance to therapy, while the endothelium, through production of angiocrine factors, is deeply involved in resistance of ovarian cancer cells to platinum and taxane based therapy.Here, we set forth the idea that disrupting the relationship between ovarian cancer cells and their host stroma constitute a new therapeutic window.