Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising of cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicities and resistivity in the long run. Nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicities. GANT61 and curcumin were co-delivered via polymeric nanoparticles for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single emulsion solvent evaporation method for the preparation of the therapeutic nanoparticles. The GANT61-curcumin PLGA nanoparticles were characterized for their size, shape, chemical properties, and anti-cancer cell studies were performed for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The nanoparticles induced cytotoxic effects to breast cancer cells at a mid-minimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual drug NPs thus provides a novel perspective on the aid of existing anti-cancer nano-medicine therapies to target a heterogeneous tumor mass effectively.