Breast cancer surgery plays a pivotal role in the multidisciplinary approaches. Surgical techniques and objectives are gradually shifting from tumor complete resection towards prolonging survival, improving cosmetic outcomes, and restoring the social and psychological well-being of patients. However, surgical treatment still faces challenges such as inadequate sensitivity in sentinel lymph node localization, the need to improve intraoperative tumor boundary localization imaging, postoperative scar healing, and the risk of recurrence, necessitating other adjunct measures for improvement. To address these challenges, specificity-optimized nanomedicines have been introduced into the surgical therapeutic landscape of breast cancer. In particular, this review involves starting with an overview of breast structure and the composition of the tumor microenvironment and then introducing the guiding principle and foundation for the design of nanomedicine. Moreover, we will take the order process of breast cancer surgery diagnosis and treatment as the starting point, and adaptively propose the roles and advantages of nanomedicine in addressing the corresponding issues. Furthermore, we also involved the prospects of utilizing advanced technological approaches. Overall, this review seeks to uncover the sophisticated design and strategies of nanomedicine from a clinical standpoint, address the challenges faced in surgical treatment, and provide insights into this subject matter.