The ability of a tumor to evade identification and immune-mediated mortality may be hampered by the removal of the immune cell population. Low oxygen levels during hypoxia significantly reduce T lymphocyte proliferation and activity and have also been shown to increase the mortality of T lymphocytes in solid tumors. Hypoxia has been demonstrated to increase the production of effector molecules such as granzyme B and tumor necrosis factor (TNF), hence boosting the lytic potential of CD8+ T cells. Hypoxia can aid in preventing cell death caused by T-cell activation, and in some instances can even promote tumor survival. Natural killer (NK) cells are able to kill targets without prior sensitization. In hematological malignancies, hypoxia has been demonstrated to reduce the expression of activating NKG2D receptors and induce granzyme B and intracellular perforin. Dendritic cells (DCs) are cells that collect and transmit tumor antigens to T lymphocytes via MHC glycoproteins. It has been demonstrated that hypoxia decreases the amount of plasmacytoid DCs in circulation while boosting the production of cytokines such as TNF-α and IL-6 in the bloodstream. In conjunction with immunotherapies, oxygen supplementation as an immunological adjuvant can diminish tumor hypoxia and HIF-1-driven extracellular adenosine build-up. This technique weakens the tumor suppressive cascade mediated by A2AR/A2BR in the hypoxic TME. In conjunction with established immunotherapies, oxygen supplementation can be a wise strategy. Metformin-induced decrease of oxygen consumption and restoration of hypoxia were linked with increased anti-PD-1 immunotherapy sensitivity. Combining antiangiogenic medicines with immunotherapy has promising prospects.