Hypoxia, a common feature in solid tumors, is linked to poor prognosis and resistance to treatment methods like radiation, chemotherapy, surgery, and immunotherapy. It is a significant obstacle for cancer treatment and has been the subject of extensive research in translational oncology. New approaches to overcome the hypoxia barrier include proton therapy and combination therapies including radiation and hypoxia-targeting medications. However, hypoxia is unevenly distributed and varies greatly throughout patients. It plays a significant role in the interactions between immune cells, stroma, and cancer cells, affecting the tumor microenvironment. Two types of hypoxia exist: persistent hypoxia, farthest from blood arteries, and acute hypoxia, near tumor vessels. Techniques for identifying hypoxic cells have advanced, and functional imaging-based biomarkers offer quantification of hypoxia. However, hypoxia-targeting therapies still have room for improvement. In silico models have become increasingly important in cancer research for treatment optimization and personalized therapy.