Introduction - Glioblastoma multiforme(GBM) presents a challenging endeavor in therapeutic management because of its highly aggressive tumor microenvironment(TME). This complex TME, characterized by hypoxia, nutrient deprivation, immunosuppression, stromal barriers, increased interstitial fluid pressure and the presence of the blood-brain barrier(BBB), frequently compromises the efficacy of promising therapeutic strategies. Consequently, a deeper understanding of the TME and the development of innovative methods to overcome its associated challenges are essential for improving treatment outcomes in GBM.