The use of hybrid nanostructures based on magneto-luminescent properties is a promising strategy for nano–bio applications and theranostics platforms. In this work, we carried out the synthesis and functionalization of iron oxide nanocubes (IONCs) to obtain multifunctional hybrid nanostructures towards biomedical applications. The IONCs were functionalized with tetraethylorthosilicate, thenoyltrifluoroacetone-propyl-triethoxysilane and europium(III)–dibenzoylmethane complexes to obtain the materials termed as IOCNCs@SiO₂, IONCs@SiO₂TTA, IONCs@SiO₂TTA–Eu and IONCs@SiO₂–TTA–Eu–DBM, respectively. Then, the biological interactions of these nanostructures with red blood cells – RBCs (hemolysis) and human blood plasma (protein corona formation) were evaluated. The XPS spectrocopy and EDS chemical mapping analysis showed that each domain is homogeneously occupied in the hybrid material, with the magnetic core at the center and the luminescent domain on the surface of the hybrid nanomaterial with a core@shell like structure. Futhermore, after each functionalization step, the nanomaterial surface charge drastically changed, with critical impact on RBC lysis and corona formation. While IONCs@SiO₂ and IONCs@SiO₂–TTA–Eu–DBM showed hemolytic properties in a dose-dependent manner, the IONCs@SiO₂TTA–Eu did not present any hemolytic effect up to 300 μg mL⁻¹. Protein corona results showed a pattern of selective adsorption of proteins with each surface of the synthesized hybrid materials. However, as a general result, a suppression of hemolysis after protein corona formation in all tests was verified. Finally, this study provides a solid background for further applications of these hybrid magneto-luminescent materials containing new surface functionalities in the emerging field of medical nanobiotechnology.