The ascent in cancer cases is startling, with breast cancer epidemiology extending across the globe. The severity of the aggressiveness of the disease is abetted by many aspects that have a critical impact on breast cancer biology, of which hypoxia is one. There is documentation of its disparate implications that defines its far-reaching impact on the therapeutic regimen. Nanomedicine mediated therapy has been seen to alleviate the adverse impact of hypoxic tumors, which has been backed by many investigative studies. This chapter entails the elemental understanding of hypoxia, its serious fall back on disease presentation, and also acknowledges the resistance to cancer cells along with its consequential impact on the disease prognosis. In this wake, this chapter recapitulates the studies primarily emphasizing the hypoxia-mediated nanoparticle treatment scheme that has advanced to avert this grave condition that makes the cancer therapy cumbersome. © 2022 Elsevier Inc. All rights reserved.