Glioblastoma (GBM) tumors rely on neovascularization, driven by specific tumor signals that stimulate endothelial cell (EC) proliferation, migration, and differentiation. Moreover, extracellular vesicles (EVs) has emerged as a key mediator in tumor angiogenesis. This in vitro study assesses glioblastoma-derived EVs' (GD-EV) potential in endothelial cell remodelling (ECR). Glioblastoma cell (U87 MG) conditioned media, treated with the chemotherapeutic drug, Temozolomide (TMZ), EV inhibitor (GW4869), or TMZ+EV inhibitor, were incubated with endothelial cells, HUVEC. Dose-& time-dependent studies were performed to demonstrate the optimal potential of GD-EVs in mediating ECR events (cell migration, proliferation, tube formation assays). Molecular mediators involved in endothelial cell remodelling such as VEGF, VEGFR, MMP2, MMP9 were identified by quantitative real-time PCR (qRT-PCR). In silico analyses were carried out using TCGA, STRING and EXOcarta databases to study the EV tetraspanins and angiogenic regulators involved in ECR. Here, we showed that conditioned media derived from U87 glioblastoma cells treated with TMZ+ EV inhibitor significantly altered the endothelial cell migration, cell proliferation. Morphological studies involving tube formation via inducing filopodia formation were carried out to demonstrate GD-EV's potential in establishing ECR. We also noted high-confidence protein clusters linking VEGF with EV biomarkers (NRP1, PECAM1, FLT1), indicating a connection between VEGF regulation and EV biogenesis/release. Additionally, significant correlations were observed between MMP2, MMP9, and EV tetraspanins, suggesting the potential involvement of EVs in triggering endothelial cell remodeling in GBM neovascularization. Preliminary results suggest that GD-EVs may have the potential to mediate the endothelial cell remodelling to promote tumour angiogenesis and tumour invasiveness.