The article discusses the potential of combining antiangiogenic therapies with immunotherapy to enhance cancer treatment. Antiangiogenic drugs target proangiogenic factors like VEGF and ANG2, which are involved in tumor growth and immune evasion. By normalizing the tumor vasculature, these drugs can improve the infiltration of immune cells into tumors and convert the immunosuppressive tumor microenvironment (TME) into an immunostimulatory one. This normalization can enhance the effectiveness of immunotherapy, particularly immune checkpoint inhibitors (ICBs), and reduce the risk of immune-related adverse effects. Tumor vasculature is abnormal and heterogeneous, leading to hypoxia, low pH, and high interstitial fluid pressure, which impair the effectiveness of various anticancer therapies, including immunotherapy. Normalizing the TME can improve the outcomes of standard and emerging anticancer therapies, including chemotherapy, radiation, molecularly targeted agents, and immunotherapies. The article highlights the potential of antiangiogenic agents to improve immunotherapy outcomes by normalizing the TME and enhancing immune cell infiltration. VEGF and ANG2 play key roles in tumor immune evasion and progression. Antiangiogenic agents can normalize the TME by reducing tumor hypoxia and improving immune cell function. The combination of antiangiogenic agents with ICBs can enhance the effectiveness of immunotherapy and improve patient outcomes. However, challenges remain, including the risk of immune-related adverse events and the need for optimal dosing and scheduling of antiangiogenic agents. The article also discusses the role of ANG2 in promoting tumor immunosuppression and metastasis. While anti-VEGF therapy can normalize tumor vessels, high doses may lead to excessive pruning and worsen hypoxia. The combination of anti-VEGF and ANG2 inhibitors may be more effective than either alone in some tumor models. However, clinical trials have shown mixed results, with some agents failing to improve patient outcomes. The article emphasizes the importance of understanding the interactions between VEGF and ANG2 signaling to develop novel strategies for preventing and treating metastasis and improving the effectiveness of immunotherapy. It also highlights the need for further research into the optimal dosing and scheduling of antiangiogenic agents and the potential of combining them with ICBs to enhance therapeutic outcomes. The findings suggest that careful mechanistic studies and biomarker-driven clinical trial designs are essential for the successful translation of dual anti-VEGF–ANG2 therapy into clinical practice.The article discusses the potential of combining antiangiogenic therapies with immunotherapy to enhance cancer treatment. Antiangiogenic drugs target proangiogenic factors like VEGF and ANG2, which are involved in tumor growth and immune evasion. By normalizing the tumor vasculature, these drugs can improve the infiltration of immune cells into tumors and convert the immunosuppressive tumor microenvironment (TME) into an immunostimulatory one. This normalization can enhance the effectiveness of immunotherapy, particularly immune checkpoint inhibitors (ICBs), and reduce the risk of immune-related adverse effects. Tumor vasculature is abnormal and heterogeneous, leading to hypoxia, low pH, and high interstitial fluid pressure, which impair the effectiveness of various anticancer therapies, including immunotherapy. Normalizing the TME can improve the outcomes of standard and emerging anticancer therapies, including chemotherapy, radiation, molecularly targeted agents, and immunotherapies. The article highlights the potential of antiangiogenic agents to improve immunotherapy outcomes by normalizing the TME and enhancing immune cell infiltration. VEGF and ANG2 play key roles in tumor immune evasion and progression. Antiangiogenic agents can normalize the TME by reducing tumor hypoxia and improving immune cell function. The combination of antiangiogenic agents with ICBs can enhance the effectiveness of immunotherapy and improve patient outcomes. However, challenges remain, including the risk of immune-related adverse events and the need for optimal dosing and scheduling of antiangiogenic agents. The article also discusses the role of ANG2 in promoting tumor immunosuppression and metastasis. While anti-VEGF therapy can normalize tumor vessels, high doses may lead to excessive pruning and worsen hypoxia. The combination of anti-VEGF and ANG2 inhibitors may be more effective than either alone in some tumor models. However, clinical trials have shown mixed results, with some agents failing to improve patient outcomes. The article emphasizes the importance of understanding the interactions between VEGF and ANG2 signaling to develop novel strategies for preventing and treating metastasis and improving the effectiveness of immunotherapy. It also highlights the need for further research into the optimal dosing and scheduling of antiangiogenic agents and the potential of combining them with ICBs to enhance therapeutic outcomes. The findings suggest that careful mechanistic studies and biomarker-driven clinical trial designs are essential for the successful translation of dual anti-VEGF–ANG2 therapy into clinical practice.