Glioblastoma multiforme (GBM) is one of the most lethal cancers, with limited treatment options due to the blood-brain barrier (BBB), systemic toxicity, and treatment resistance. Nanomedicine offers potential solutions to these challenges. This study explores Pluronic® F127 and Soluplus®-based micelles as carriers for Lomustine, Gefitinib, and Docetaxel to determine the optimal system for GBM therapy. Micelles were physicochemically characterized and biologically validated using U87-MG and U251-MG GBM cell lines in 2D and 3D models, assessing internalization, safety, and therapeutic efficacy. Soluplus® micelles (SM) showed favorable properties for intravenous administration, including low polydispersity, efficient drug release in the tumoral microenvironment, minimal cell toxicity, and a BBB-crossing rate of 15 %. Among the drugs tested, Docetaxel showed the lowest IC