The article explores the therapeutic targeting of hypoxia-inducible factors (HIFs) in cancer treatment. HIFs play a crucial role in regulating genes that influence angiogenesis, cell proliferation, and glucose metabolism, making them significant targets for anticancer therapies. The study reviews the molecular mechanisms of HIF activation and its dysregulation in cancer, highlighting the potential of HIF inhibitors, anti-angiogenic therapies, and hypoxia-activated prodrugs. Preclinical studies have shown the efficacy of agents like EZN-2968, Mimelide, and Acrifavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of antitumor activity. However, challenges such as toxicity require further research and clinical trials to optimize these therapies. The article emphasizes the potential of targeted HIF therapies in disrupting cancer-related signaling pathways, offering a promising approach for future cancer therapeutics.The article explores the therapeutic targeting of hypoxia-inducible factors (HIFs) in cancer treatment. HIFs play a crucial role in regulating genes that influence angiogenesis, cell proliferation, and glucose metabolism, making them significant targets for anticancer therapies. The study reviews the molecular mechanisms of HIF activation and its dysregulation in cancer, highlighting the potential of HIF inhibitors, anti-angiogenic therapies, and hypoxia-activated prodrugs. Preclinical studies have shown the efficacy of agents like EZN-2968, Mimelide, and Acrifavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of antitumor activity. However, challenges such as toxicity require further research and clinical trials to optimize these therapies. The article emphasizes the potential of targeted HIF therapies in disrupting cancer-related signaling pathways, offering a promising approach for future cancer therapeutics.