Elucidation of the ecological characteristics of malignant tumors has shown that angiogenesis and an immunosuppressive status in the tumor microenvironment are important for resolving treatment resistance and poor prognosis. Vascular endothelial growth factor(VEGF) and components of related signaling pathway can be targeted by anti-angiogenic therapy. Suppression of abundant angiogenesis using anti-angiogenic agents in high-grade gliomas inhibits rapid neurological deterioration in patients. Additionally, as VEGF promotes the formation of an immunosuppressive tumor microenvironment, anti-angiogenic therapy is expected to contribute to improving the immune status in the tumor microenvironment. In this review, we discuss the role of VEGF-targeted therapy and immunotherapy targeting immune checkpoint inhibitors and macrophages in high-grade gliomas. The authors also discuss the possibility of using these as combination therapies.