Abstract <p>Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide, despite significant advances in early detection and treatment. Conventional chemotherapeutic agents often face limitations such as drug resistance, off-target toxicity, and poor patient adherence. These challenges have highlighted the need for safer, more effective alternatives. Naturally derived compounds, especially flavonoids such as quercetin, have recently attracted attention for their ability to modulate key cancer pathways with minimal side effects. This review critically examines natural quercetin and its metabolites in the context of breast cancer prevention and treatment, focusing on their molecular targets and pharmacodynamic effects. To address issues such as poor bioavailability and rapid metabolism, we also discuss the design and synthesis of quercetin derivatives that exhibit improved stability, solubility, and targeted delivery. Additionally, the review highlights emerging quercetin-based nanomaterials designed to enhance therapeutic precision. This review offers a comprehensive overview of the development of quercetin-based therapies, outlining current progress, identifying translational hurdles, and proposing future directions for the development of optimized, targeted, and clinically viable quercetin formulations for breast cancer treatment.</p> Graphical asbstract <p>Quercetin shows strong anticancer potential against breast cancer by modulating key pathways. Advances in its formulation improve stability and delivery, helping overcome drug resistance and offering promising future therapeutic applications.</p> <p></p>