The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450 (CYP450). Herein, bi-enzymatic nanoreactors (NRs) are developed as a multimodality platform for smart action against breast tumors. CYPBM3 of Bacillus magaterium (CYP) is co-confined with glucose oxidase (GOx) where GOx produces H2O2 in the presence of glucose that elicits the CYP-mediated transformation of tamoxifen. The scintillating and mesoporous LaF3:Tb as nanocarrier showed advantages like a wide range of pore size and positive surface charge for efficient loading of enzyme couple, while the smallest pores were available for substrate/product diffusion. The obtained NRs were camouflaged with human serum albumin (HSA) to overcome premature enzyme leaching and provide active stealth properties. The nanocomposite was characterized for physicochemical properties and glucose-mediated sequential catalysis. The in vitro studies demonstrated the cell internalization of NRs in both ER+ and triple-negative breast cancer cell lines and showed significant cytotoxicity. The developed NRs not only improve the outcomes of endocrine therapy in ER+ cells but also synergistically act with oxidation therapy for enhanced therapeutic effect. Importantly, inhibition of triple-negative cells was also achieved. Thus, the development of the new multimodal nanomedicine of the present work should afford new tools towards the theranosis of breast cancer with minimized adverse effects. (C) 2020 Elsevier Inc. All rights reserved.