Innovative treatment strategies are required for breast cancer, which continues to be a major worldwide health concern. Because of how intricately signaling pathways interact, they are essential targets for cutting-edge treatments. This chapter investigates the possibility of natural substances as therapeutic agents that alter these pathways in treating breast cancer. The chapter starts by providing a summary of the crucial signaling pathways involved in the advancement of breast cancer, including the PI3K/AKT, MAPK, and Wnt/β-catenin pathways. These pathways influence cellular survival, metastasis, and drug resistance, making them prime candidates for therapeutic intervention. Natural substances from different botanical and marine sources have drawn interest for their wide range of bioactive characteristics. The chapter dives into the processes by which these substances affect cells, including kinase inhibition, receptor modification, and apoptosis induction. Their potential to interfere with oncogenic signaling cascades may be seen by carefully examining how they interact with certain pathways. The chapter summarizes preclinical and clinical research examining the effects of natural substances, with a focus on specific signaling pathways. Research shows that they can reduce pathway activation, stop the development of tumors, and make cancer cells more responsive to already available treatments. It also highlights their potential for increased effectiveness and less toxicity to explore synergistic combinations with traditional medicines. A growing field of research is the conversion of natural substances into clinical trials. The chapter offers insights into current studies and discusses potential and obstacles in determining how safe and effective they are for people with breast cancer. By affecting important signaling pathways, natural substances provide a possible route for targeted breast cancer treatment. They provide opportunities for individualized and comprehensive treatment approaches due to their complex processes and possible synergy. To emphasize the significance of responsible resource consumption, ethical issues, and sustainable sourcing are also covered. Integration of natural substances into conventional oncology has a lot of potential for upgrading breast cancer therapy paradigms, provided study and cooperation continue.