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Glioblastoma (GBM) is one of the most aggressive and deadliest central nervous system tumors, and the current standard treatment is surgery followed by radiotherapy with concurrent chemotherapy. Nevertheless, the survival period is notably low. Although ample research has been performed to develop an effective therapeutic strategy for treating GBM, the success of extending patients’ survival period and quality of life is limited. This review focuses on the strategies developed to address the challenges associated with drug delivery in GBM, particularly nanomedicine. The first part describes major obstacles to the development of effective GBM treatment strategies. The second part focuses on the conventional chemotherapeutic nanomedicine strategies, their limitations and the novel and advanced strategies of nanomedicine, which could be promising for GBM treatment. We also highlighted the prominence of nanomedicine clinical translation. The near future looks bright following the beginning of clinical translation of nanochemotherapy for GBM.