Abstract: Breast cancer is the most prevalent malignant tumor in women globally, with a significant and growing number of new cases each year. Accurately defining the boundaries of breast cancer lesions in imaging poses a significant challenge for evaluating the tumor’s size, morphology, invasion range, and relationship with surrounding tissues. In spite of the limitations in identifying the boundaries of breast cancer lesions for traditional imaging methods, the booming development of omics, combined with nanoscale contrast agents, provides abundant target information and molecular mechanism basis for the precise identification of breast cancer lesion boundaries. This review summarizes the results of omics-based analysis on the features of breast cancer lesion boundaries, and discusses through detailed classification the design principles, ideas, and applications of nanoscale contrast agents for imaging breast cancer lesion boundaries according to different imaging strategies, with also a summary of the current challenges and limitations in this field along with prospects for future development.