In this study, we aimed to improve the delivery and efficacy of the well‐known anticancer drug, tamoxifen (TAM), through its encapsulation in bovine serum albumin nanoparticles (BSA NPs) and their hybridization with selenium nanoparticles (Se NPs). The developed nanostructures were characterized by Fourier transform infrared (FT‐IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, energy‐dispersive X‐ray spectroscopy (EDS) analysis, dynamic light scattering (DLS), and field emission scanning electron microscopy (FESEM) imaging. The impact of nanostructures on 4T‐1 cancer cells was assessed through MTT and flow cytometry assays to measure cytotoxicity and apoptosis rates, respectively. FT‐IR and UV–Vis spectroscopy confirmed the successful encapsulation of TAM within BSA NPs. EDS analysis confirmed the Se integration into BSA‐TAM@Se NPs, signifying successful hybridization. Size and zeta potential measurements revealed the average hydrodynamic size and surface charge of the nanostructures. BSA NPs, BSA@Se NPs, and Se NPs showed the sizes ranging from 153.37 ± 1.02 to 229.63 ± 1.36 nm, with zeta potential values from −10.12 ± 0.26 to −28.45 ± 0.40 mV. Hemocompatibility studies demonstrated minimal hemolytic activity of the nanostructures, indicating their biocompatibility for intravenous administration. Cellular toxicity assays showed higher cytotoxicity of BSA‐TAM@Se NPs compared to other formulations (****p < 0.0001). The increased cell death in 4T‐1 breast cancer cells highlights the enhanced therapeutic potential of BSA‐TAM@Se NPs. Apoptosis analysis revealed a significant increase in apoptosis rate in 4T‐1 cells treated with BSA‐TAM@Se NPs compared to other formulations (****p < 0.0001), emphasizing their ability to induce programmed cell death. These findings support the rational importance of BSA NPs as drug nanocarriers and their hybridization with Se NPs to improve therapeutic effects. Finally, we suggest that the developed BSA‐TAM@Se NPs can be used as a potential therapeutic approach in combination with other tools such as X‐ray irradiation in future studies.