The article provides an in-depth review of the glioblastoma (GB) tumor microenvironment (TME) and discusses current and emerging therapeutic approaches. GB is the most common and aggressive form of brain cancer, characterized by high-grade astrocytoma with microvascular proliferation, invasiveness, and necrosis. The TME is highly complex and dynamic, involving various components such as the blood-brain barrier (BBB), immune cells, and non-immune cells. The BBB, a specialized structure regulating molecular exchange between the blood and brain, becomes leaky in GB due to factors like VEGF and MMPs, leading to increased permeability and chronic inflammation. Immune cells, including macrophages, microglia, T cells, B cells, NK cells, dendritic cells, and myeloid-derived suppressor cells (MDSCs), play crucial roles in tumor progression and immune suppression. Non-immune cells like endothelial cells, astrocytes, and neurons also contribute to GB development and drug resistance. Single-cell sequencing has revolutionized understanding of GB heterogeneity, revealing the importance of tumor-associated fibroblasts (CAFs). Angiogenesis, driven by growth factors like VEGF, FGF, PDGF, HGF, and Angiopoietins, is a critical process for GB growth. Therapeutic approaches include adaptive T cell therapies, checkpoint inhibitors, angiogenesis inhibitors, vaccines, and signaling pathway targets. Checkpoint inhibitors, such as PD-1 and TIM-3 inhibitors, have shown promise in clinical trials. Angiogenesis inhibitors like bevacizumab target VEGF, while vaccines targeting EGFRvIII, a common mutation in GB, are under investigation. Understanding and targeting these components offer potential strategies for improving GB treatment outcomes.The article provides an in-depth review of the glioblastoma (GB) tumor microenvironment (TME) and discusses current and emerging therapeutic approaches. GB is the most common and aggressive form of brain cancer, characterized by high-grade astrocytoma with microvascular proliferation, invasiveness, and necrosis. The TME is highly complex and dynamic, involving various components such as the blood-brain barrier (BBB), immune cells, and non-immune cells. The BBB, a specialized structure regulating molecular exchange between the blood and brain, becomes leaky in GB due to factors like VEGF and MMPs, leading to increased permeability and chronic inflammation. Immune cells, including macrophages, microglia, T cells, B cells, NK cells, dendritic cells, and myeloid-derived suppressor cells (MDSCs), play crucial roles in tumor progression and immune suppression. Non-immune cells like endothelial cells, astrocytes, and neurons also contribute to GB development and drug resistance. Single-cell sequencing has revolutionized understanding of GB heterogeneity, revealing the importance of tumor-associated fibroblasts (CAFs). Angiogenesis, driven by growth factors like VEGF, FGF, PDGF, HGF, and Angiopoietins, is a critical process for GB growth. Therapeutic approaches include adaptive T cell therapies, checkpoint inhibitors, angiogenesis inhibitors, vaccines, and signaling pathway targets. Checkpoint inhibitors, such as PD-1 and TIM-3 inhibitors, have shown promise in clinical trials. Angiogenesis inhibitors like bevacizumab target VEGF, while vaccines targeting EGFRvIII, a common mutation in GB, are under investigation. Understanding and targeting these components offer potential strategies for improving GB treatment outcomes.