Updated project metadata. The recent develop of nanotechnology promises to revolutionize the delivery of chemotherapeutic agents across the blood-brain barrier and against cancer cells. Superparamagnetic iron oxide nanoparticles have been successfully exploited in many different clinical trials for the remote hyperthermal treatment of cancer cells in response to alternated magnetic fields (AMF) and as nontargeted contrast agents for magnetic resonance imaging (MRI). In this work, the functionalization of SPIONs- and TMZ-loaded lipid magnetic nanovectors (LMNVs) with the antibody against the transferrin receptor (TfR) for the dual targeting of the endothelial cells of BBB and GBM cells is reported. The targeting efficiency of the functionalized nanovectors (AbLMNVs) has been demonstrated on a multicellular organoid system modeling the BBB and the microscopic GBM foci. Transcytosis through endothelial cells and penetration in GBM spheroids of functionalized nanovectors have been verified and quantified through flow cytometry analysis and different imaging techniques. Moreover, the lipid component of the functionalized nanovectors has been modified with a lipophilic temperature sensitive fluorescent dye to monitor the intraparticle temperature in response to AMF Chronic AMF treatments of microscopic GBM spheroids targeted with the functionalized nanovectors, plain or loaded with TMZ drug, were carried out and their elevated potential to induce spheroid disintegration, cell necrosis and apoptosis was revealed. Finally, magnetothermal ability of nanovectors was successfully tested on a post-mortem brain tissue.