Nanoparticle-based combinatorial strategies are promising approaches to overcome the blood-brain barrier (BBB) and blood-tumor barrier (BTB) for effective drug delivery to glioblastoma multiforme (GBM). These strategies combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic fields, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery uses engineered cells as carriers for nanoparticles, leveraging their migratory and homing capabilities to transport therapeutic payloads across the BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, combined with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery uses magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive route to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM. Keywords: glioblastoma, blood-brain barrier, blood-tumor barrier, nanoparticle, combination strategy, ultrasound-wave, magnetic field, intranasal drug delivery.Nanoparticle-based combinatorial strategies are promising approaches to overcome the blood-brain barrier (BBB) and blood-tumor barrier (BTB) for effective drug delivery to glioblastoma multiforme (GBM). These strategies combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic fields, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery uses engineered cells as carriers for nanoparticles, leveraging their migratory and homing capabilities to transport therapeutic payloads across the BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, combined with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery uses magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive route to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM. Keywords: glioblastoma, blood-brain barrier, blood-tumor barrier, nanoparticle, combination strategy, ultrasound-wave, magnetic field, intranasal drug delivery.