The age of cancer as an isolated single-cell concept is now behind us. It is now established that epithelial ovarian cancer, like other cancers, interacts with the healthy bystander cells to influence them and takes advantage of their nutritional, immunological, disseminating and other capacities. This interaction has become a therapeutic target, as shown by the numerous studies on this subject. Intraperitoneal chemo-hyperthermia has been part of the therapeutic armamentarium for some time yet its efficiency in ovarian cancer has only been recently proven in a randomized controlled trial. However, its therapeutic performance is not revolutionary and epithelial ovarian cancer maintains a high mortality. In this review, we studied the impact of HIPEC on the microenvironment and vice versa to determine whether it could be the key to this lukewarm efficacy. We began by exploring the modalities of HIPEC and establishing the reasons that make this treatment topical. Then, we examined its impact on each element of the tumor environment to obtain a global view of the resistance mechanisms at work in HIPEC.