Glioblastoma (GBM) remains one of the most aggressive malignancies of the central nervous system. Its treatment faces significant hurdles due to the blood-brain barrier (BBB), the profoundly immunosuppressive tumor microenvironment (TME), and inherent tumor heterogeneity, which limit the efficacy of current immunotherapies, including immune checkpoint inhibitors. This has shifted focus towards harnessing the innate immune system, particularly the cGAS-STING pathway. As a critical sensor of cytosolic DNA and a central hub for type I interferon (IFN-I) production, this pathway plays a vital role in initiating anti-tumor immunity. However, its activity is often suppressed in GBM through mechanisms such as epigenetic silencing of the STING gene promoter and extracellular cyclic GMP-AMP degradation. Recently, nanomaterials have emerged as advanced drug delivery systems offering novel strategies to overcome these obstacles. This review aims to systematically summarize the biological functions of the cGAS-STING pathway, the key factors contributing to its suppression in GBM, and critically evaluates the advancements in utilizing nanomaterials for crossing the BBB, achieving targeted delivery, intracellular release, and environment-responsive regulation of STING agonists. Furthermore, it delves into how nanotechnology-based STING pathway activation strategies can synergize with existing therapies like immune checkpoint blockade, tumor vaccines, radiotherapy, and chemotherapy to enhance anti-tumor efficacy, overcome immunosuppression, and induce durable immune memory. Finally, this review outlines the major challenges currently facing the field (including in vivo delivery assessment, biosafety, and personalized therapeutic approaches), intending to provide insights for the development of more effective immunotherapy strategies against GBM.