Background: The most common and deadly cancer in female is breast cancer (BC) and new incidence and deaths related to this cancer are rising. Aims: Several issues, that is, high cost, toxicity, allergic reactions, less efficacy, multidrug resistance, and the economic cost of conventional anti-cancer therapies, has prompted scientists to discover innovative approaches and new chemo-preventive agents. Materials: Numerous studies are being conducted on plant-based and dietary phytochemicals to discover new-fangled and more advanced therapeutic approaches for BC management. Result: We have identified that natural compounds modulated many molecular mechanisms and cellular phenomena, including apoptosis, cell cycle progression, cell proliferation, angiogenesis and metastasis, up-regulation of tumor-suppressive genes, and down-regulation of oncogenes, modulation of hypoxia, mammosphere formation, onco-inflammation, enzymatic regulation, and epigenetic modifications in BC. We found that a number of signaling networks and their components such as PI3K/Akt/mTOR, MMP-2 and 9, Wnt/-catenin, PARP, MAPK, NF-κB, Caspase-3/8/9, Bax, Bcl2, Smad4, Notch1, STAT3, Nrf2, and ROS signaling can be regulated in cancer cells by phytochemicals. They induce up-regulation of tumor inhibitor microRNAs, which have been highlighted as a key player for ani-BC treatments followed by phytochemical supplementation. Conclusion: Therefore, this collection offers a sound foundation for further investigation into phytochemicals as a potential route for the development of anti-cancer drugs in treating patients with BC.