Hesperidin, a natural compound abundant in citrus fruits, shows promise in breast cancer management due to its safety and diverse mechanisms of action. This review explores hesperidin's origin, chemical properties, and its ability to inhibit cell proliferation through various pathways. While hesperidin alone has limited efficacy against breast cancer, it demonstrates synergistic effects when combined with other compounds. Formulation strategies to enhance hesperidin's efficacy include improving solubility, stability, and absorption for targeted delivery. Combisomes, liposomal delivery systems encapsulating hesperidin and anticancer compounds, offer a potentially efficacious and safe platform. They target cancer cells specifically, minimizing adverse effects on healthy cells. Hesperidin's ability to induce cell cycle arrest, apoptosis, and modulate PD-L1 expression contributes to its anticancer effects. Combining hesperidin with other agents enhances its therapeutic potential. Overall, hesperidin emerges as a promising candidate for breast cancer treatment, with formulation enhancements and innovative delivery systems like combisomes offering significant advancements in therapeutic strategies. Further research into hesperidin's efficacy and safety, especially in combination therapies, is warranted for its potential translation into clinical practice.