Cancer therapeutics development has been a challenge due to their untoward side effects and cytotoxicity. Phytochemical anti-cancer drugs have several advantages over chemical chemotherapeutic drugs as they are less cytotoxic and have a greater pharmacological advantage. However, lack of targeting ability limits the use of phytochemicals at a great extent for a successful therapeutic strategy. Gold nanoparticles (AuNPs) have long been used to load the therapeutic cargo and provided significant advantages over conventional chemo-therapeutics. In this present study, we report the synthesis and testing of various biosynthesized AuNPs (b-AuNPs) using naturally derived phytochemicals (Curcumin: Cur, Turmeric: Tur, Quercetin: Qu and Paclitaxel: Pacli). The synthesized b-AuNPs have been well characterized by different Physicochemical techniques. Cytotoxic potential of these b-AuNPs were evaluated in different breast cancer cells either in an individual or in a combination forms. We have observed the maximum therapeutic activity in a combination of all four types of b-AuNPs (AuNPs-Cur, AuNPs-Tur, AuNPs-Qu and AuNPs-Pacli) as compared to their pristine administration. Further, mechanistic studies of these compounds revealed that, combinations of AuNPs-Cur, AuNPs-Tur, AuNPs-Qu and AuNPs-Pacli were significantly effective in inhibiting cell proliferation, apoptosis, angiogenesis, colony formation and spheroid formation predicting a synergistic effect when compared to individual treatment against different breast cancer cell lines (MCF-7 and MDA-MB 231). Interestingly the nanoconjugates alone or in combinations did not show cytotoxicity towards human embryonic normal kidney cell line (HEK 293), demonstrating the biocompatibility. Together the results demonstrated the potential anti-cancer properties of b-AuNPs in a combinatorial approach that could be the future of cancer nanomedicine.