Glioblastoma (GBM) is the most prevalent and aggressive form of brain cancer, characterized by its immunosuppressive microenvironment, which hinders conventional therapeutic interventions. Despite established treatments such as surgery, radiotherapy, chemotherapy, and emerging modalities like immunotherapy, the efficacy remains suboptimal, leading to poor prognoses. Recent studies have highlighted the significance of cellular components within the GBM microenvironment, particularly myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAMs), and regulatory T cells (Tregs), in fostering immune evasion and tumor progression. MDSCs, despite being a minority (4-8%) of CD45+ cells in GBM, play a central role in promoting angiogenesis, invasion, and metastasis through intricate immunosuppressive mechanisms. Understanding the interplay between GBM and MDSCs provides a basis for therapeutic interventions. This review explores the immune regulatory mechanisms in the GBM microenvironment, existing therapeutic targets, and recent insights into MDSC induction and their contribution to immunosuppression. It also surveys ongoing clinical trials and potential treatment strategies, aiming to integrate immunotherapy with other modalities to improve patient outcomes and quality of life.Glioblastoma (GBM) is the most prevalent and aggressive form of brain cancer, characterized by its immunosuppressive microenvironment, which hinders conventional therapeutic interventions. Despite established treatments such as surgery, radiotherapy, chemotherapy, and emerging modalities like immunotherapy, the efficacy remains suboptimal, leading to poor prognoses. Recent studies have highlighted the significance of cellular components within the GBM microenvironment, particularly myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAMs), and regulatory T cells (Tregs), in fostering immune evasion and tumor progression. MDSCs, despite being a minority (4-8%) of CD45+ cells in GBM, play a central role in promoting angiogenesis, invasion, and metastasis through intricate immunosuppressive mechanisms. Understanding the interplay between GBM and MDSCs provides a basis for therapeutic interventions. This review explores the immune regulatory mechanisms in the GBM microenvironment, existing therapeutic targets, and recent insights into MDSC induction and their contribution to immunosuppression. It also surveys ongoing clinical trials and potential treatment strategies, aiming to integrate immunotherapy with other modalities to improve patient outcomes and quality of life.