The majority of the human brain consists of glial cells. Gliomas are tumours arising from glia. High-grade gliomas called glioblastomas (GBM) account for 59.5% of CNS tumours in India. GBMs exhibit poor morbidity of <15months. A sound understanding of glioma pathophysiology is critical to device diagnostics or treatment strategies. The current gold standard to study GBM utilizes patient-derived cell lines. However, these lack emulation of in vivo tumour physiology. The lacunae arise in both, the cell culture techniques employed and the limited extrapolation from animal models. Novel 3D co-cultured spheroids consist of cell aggregates that capture the native architecture of in vivo tumours, growth factors, metabolic gradients, microenvironment, and cell-cell interactions. Therefore, 3D culture approaches overcome these pitfalls by recapitulating human physiology (cellular morphology, phenotype, and gene expression). 3D spheroids have proven to be an apt resource to investigate cellular interactions within tumours. They are a cost-effective option for large-scale testing of drug candidates.