This article provides an overview of the glioblastoma (GB) tumor microenvironment and current and emerging therapeutic approaches. GB is a highly aggressive and recurrent primary brain tumor with low survival rates. The tumor microenvironment plays a critical role in GB progression, promoting tumor heterogeneity, angiogenesis, and immune evasion. The microenvironment consists of various immune and non-immune components, including microglia, macrophages, T cells, B cells, natural killer (NK) cells, dendritic cells, and myeloid-derived suppressor cells, as well as non-immune components such as the extracellular matrix, endothelial cells, astrocytes, and neurons. The tumor microenvironment is complex and dynamic, contributing to the poor prognosis of GB and making it a challenging target for therapeutic interventions. Current therapeutic approaches target the regulators of the tumor microenvironment through both generalized and personalized strategies. The review summarizes important milestones in GB research, factors regulating the tumor microenvironment, and potential therapeutic agents used in GB treatment. The blood-brain barrier (BBB) is a critical component of the GB microenvironment, regulating the flow of molecules between the blood and the brain. However, GB tumors often lead to BBB disruption, increasing permeability and allowing the entry of immune cells and carcinogenic chemicals into the tumor microenvironment. This can promote tumor development and spread, while also limiting the delivery of therapeutic drugs to the brain. The tumor microenvironment is also characterized by the presence of various immune cells, including macrophages, microglia, T cells, B cells, NK cells, and dendritic cells, which can either promote or suppress tumor growth. Macrophages, for example, can have both pro- and anti-tumor effects depending on their polarization state. Tumor-associated macrophages (TAMs) are known to promote tumor growth and angiogenesis by secreting cytokines and growth factors such as VEGF. Similarly, microglia can contribute to tumor progression by secreting pro-angiogenic factors and suppressing anti-tumor immune responses. The tumor microenvironment also includes non-immune cells such as endothelial cells, astrocytes, and neurons, which play important roles in tumor development, angiogenesis, and immune evasion. Endothelial cells are crucial for angiogenesis, which is a key process in GB growth. Astrocytes can produce immunomodulatory substances such as TGF-β and IL-10, which can dampen the immune response to GB cells. Neurons in the GB microenvironment have also been shown to contribute to tumor formation by promoting GB cell motility and invasion. Emerging therapeutic approaches for GB include immunotherapy, angiogenesis inhibitors, and vaccine-based strategies. Immunotherapy, such as checkpoint inhibitors targeting PD-1 and PD-L1, has shown promise in preclinical studies and is being investigated in clinical trials. Angiogenesis inhibitors, such as bevacizumab, target VThis article provides an overview of the glioblastoma (GB) tumor microenvironment and current and emerging therapeutic approaches. GB is a highly aggressive and recurrent primary brain tumor with low survival rates. The tumor microenvironment plays a critical role in GB progression, promoting tumor heterogeneity, angiogenesis, and immune evasion. The microenvironment consists of various immune and non-immune components, including microglia, macrophages, T cells, B cells, natural killer (NK) cells, dendritic cells, and myeloid-derived suppressor cells, as well as non-immune components such as the extracellular matrix, endothelial cells, astrocytes, and neurons. The tumor microenvironment is complex and dynamic, contributing to the poor prognosis of GB and making it a challenging target for therapeutic interventions. Current therapeutic approaches target the regulators of the tumor microenvironment through both generalized and personalized strategies. The review summarizes important milestones in GB research, factors regulating the tumor microenvironment, and potential therapeutic agents used in GB treatment. The blood-brain barrier (BBB) is a critical component of the GB microenvironment, regulating the flow of molecules between the blood and the brain. However, GB tumors often lead to BBB disruption, increasing permeability and allowing the entry of immune cells and carcinogenic chemicals into the tumor microenvironment. This can promote tumor development and spread, while also limiting the delivery of therapeutic drugs to the brain. The tumor microenvironment is also characterized by the presence of various immune cells, including macrophages, microglia, T cells, B cells, NK cells, and dendritic cells, which can either promote or suppress tumor growth. Macrophages, for example, can have both pro- and anti-tumor effects depending on their polarization state. Tumor-associated macrophages (TAMs) are known to promote tumor growth and angiogenesis by secreting cytokines and growth factors such as VEGF. Similarly, microglia can contribute to tumor progression by secreting pro-angiogenic factors and suppressing anti-tumor immune responses. The tumor microenvironment also includes non-immune cells such as endothelial cells, astrocytes, and neurons, which play important roles in tumor development, angiogenesis, and immune evasion. Endothelial cells are crucial for angiogenesis, which is a key process in GB growth. Astrocytes can produce immunomodulatory substances such as TGF-β and IL-10, which can dampen the immune response to GB cells. Neurons in the GB microenvironment have also been shown to contribute to tumor formation by promoting GB cell motility and invasion. Emerging therapeutic approaches for GB include immunotherapy, angiogenesis inhibitors, and vaccine-based strategies. Immunotherapy, such as checkpoint inhibitors targeting PD-1 and PD-L1, has shown promise in preclinical studies and is being investigated in clinical trials. Angiogenesis inhibitors, such as bevacizumab, target V