Introduction: High-throughput profiling of cancer tissue specimens and body fluids has been used extensively to reveal specific molecular fingerprints of breast cancer. Women with breast cancer are associated with several modifiable and non-modifiable risk factors. Despite the major advances made in the field of breast cancer screening and therapeutics, it remains a major health issue and a key cause of mortality for women across the globe. Especially, the off-target properties of chemotherapeutic agents remain the main concern. Being a good potential chemotherapeutic, the compound should target the rapidly dividing cancer cells, eventually create less cytotoxicity to normal cells. Aim: To do so, in our present study, we have studied the anti-cancer potentiality of Lycopersicon esculentum fruits and Cassia fistula pods in vitro breast cancer cells and compared their anti-cancer efficacy too. Methodology: Plant extracts were noted to be non-toxic to normal breast epithelial cells but toxic to breast cancer cells. How ever, the ethyl acetate extract of the Lycopersicon esculentum fruits was most effective amongst all other extracts. Results: Data suggest that Lycopersicon esculentum fruits potentiate DNA damage mediated apoptosis and negatively regulate cell proliferation, angiogenesis and metastasis in vitro and in vivo. Moreover, the anti-cancer phenomenon was found to be the induction of inflammatory cytokines mediated oxidative stress in breast cancer. Conclusion: Lycopersicon esculentum fruits and Cassia fistula pods show excellent cancer therapeutics to induce DNA damage, inhibit angiogenesis and metastasis simultaneously.