Novel antibody-drug conjugates are profoundly changing treatment strategies and concepts of disease classification in breast cancer. Among these, breast cancer with low HER2 expression historically had a poor prognosis due to the lack of effective targeted therapies. Antibody-drug conjugates, represented by trastuzumab deruxtecan, have significantly improved survival outcomes in patients with HER2-low breast cancer across multiple key clinical studies, prompting updates in treatment guidelines and expansion of indications. This article systematically reviews the clinicopathological characteristics and heterogeneity-related challenges of HER2-low breast cancer, with a focus on the clinical applications and mechanisms of action of new antibody-drug conjugates. It also highlights current diagnostic and therapeutic limitations and suggests in future research directions, thereby providing a theoretical basis for more precise patient stratification and treatment.