Glioblastoma (GBM) is the most frequent and most malignant brain tumour, with a dismal five-year survival rate lower than 5%. treatment is complex due to the presence of the Blood Brain Barrier (BBB), the high genomic variability, and the heterogeneity of the tumour microenvironment (TME). Moreover, the presence of a cancer stem cell (CSCs) niche drives the development of treatment resistance. Identifying appropriate therapeutic agents and delivery mechanisms to grant effective targeting with reduced side effects is key in improving GBM management. Unfortunately, drug screening mainly relies on ethically debated animal models or on in vitro models, which do not fully replicate the TME and other relevant phenomena such as angiogenesis or immune response.