Recently, nanoparticles (NPs) have been employed to enhance the distribution of new medications across the BBB. In this study, a synergistic nanoassembly has been prepared for magnetic resonance imaging-guided chemo-phototherapy of glioblastoma multiforme (GBM). In accordance, Fe3O4 NPs are prepared with SiO2 shell followed by the loading of an anticancerous drug temozolomide (TMZ) to generate Fe3O4 @SiO2/TMZ NPs. Later, drug-loaded NPs are coated with platelet membrane (PLTM) to develop the final biocompatible form of nanoassembly as Fe3O4 @SiO2/TMZ@PLTM NPs for synergistic therapy of GBM. We combined chemotherapy with photothermal therapy in a magnetically targeted TMZ-loaded Fe3O4 @SiO2 core-shell that was activated by near-infrared irradiation and then developed platelet membrane-coated Fe3O4 @SiO2/TMZ to improve the precise delivery of drugs into GBM cells and enable a more efficient photothermal therapy. According to the cellular uptake findings, the Fe3O4 @SiO2/TMZ@PLTM NPs possess a greater uptake compared to the uncoated Fe3O4 @SiO2/TMZ NPs owing to the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of GBM cells. Moreover, the nanoassembly has displayed a pH-responsive drug release and an excellent photothermal effect under NIR (808 nm, 1 W/cm2) irradiation. After 10 min of irradiation, the temperature has been elevated to about 65 °C leading to the death of 80% of GBM cells in vitro. Additionally, the fabricated NPs possess a remarkable contrasting property for T1-weighted magnetic resonance imaging (MRI) due to the presence of superparamagnetic iron oxide NPs. These findings demonstrate the promising theranostic behaviour of fabricated Fe3O4 @SiO2/TMZ@PLTM NPs for synergistic therapy of glioblastoma multiforme (GBM).