Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood-brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM has been restricted. Drug delivery based on nanocarriers and nanotechnology has the potential to be a handy tool in the continuing effort to combat the challenges of treating GBM. There are various new therapies being tested to extend survival time. Maximizing therapeutic effectiveness necessitates using many treatment modalities at once. In the fight against GBM, combination treatments outperform individual ones. Combination therapies may be enhanced by using nanotechnology-based delivery techniques. Nano-chemotherapy, nano-chemotherapy-radiation, nano-chemotherapy-phototherapy, and nano-chemotherapy-immunotherapy for GBM are the focus of the current review to shed light on the current status of innovative designs.