The article reviews the advancements in the treatment of breast cancer, particularly focusing on the role of human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugates (ADCs). HER2 is overexpressed in about 20% of breast cancers, leading to more aggressive disease and poorer prognosis. Traditional treatments, including chemotherapy and monoclonal antibodies like trastuzumab and pertuzumab, have shown limited efficacy due to drug resistance. ADCs, such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have emerged as promising therapeutic options, demonstrating superior clinical outcomes in HER2-positive breast cancer. However, drug resistance remains a significant challenge. The review highlights the mechanisms of resistance to T-DM1 and T-DXd, including antigen downregulation, impaired drug internalization, and efflux transporters. It also discusses the development of novel ADCs, such as disitamab vedotin (RC48), ARX788, trastuzumab duocarmazine (SYD985), BL-M0701, and zanidatamab zovodotin (ZW49), which aim to overcome these resistance mechanisms and improve patient outcomes. Clinical trials are crucial for optimizing dosing regimens, understanding resistance mechanisms, and identifying patient populations most likely to benefit from these treatments. The article concludes by emphasizing the potential of ADCs to revolutionize the treatment of HER2-positive and HER2-Low breast cancer, offering a new era of targeted therapy with improved efficacy and safety.The article reviews the advancements in the treatment of breast cancer, particularly focusing on the role of human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugates (ADCs). HER2 is overexpressed in about 20% of breast cancers, leading to more aggressive disease and poorer prognosis. Traditional treatments, including chemotherapy and monoclonal antibodies like trastuzumab and pertuzumab, have shown limited efficacy due to drug resistance. ADCs, such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have emerged as promising therapeutic options, demonstrating superior clinical outcomes in HER2-positive breast cancer. However, drug resistance remains a significant challenge. The review highlights the mechanisms of resistance to T-DM1 and T-DXd, including antigen downregulation, impaired drug internalization, and efflux transporters. It also discusses the development of novel ADCs, such as disitamab vedotin (RC48), ARX788, trastuzumab duocarmazine (SYD985), BL-M0701, and zanidatamab zovodotin (ZW49), which aim to overcome these resistance mechanisms and improve patient outcomes. Clinical trials are crucial for optimizing dosing regimens, understanding resistance mechanisms, and identifying patient populations most likely to benefit from these treatments. The article concludes by emphasizing the potential of ADCs to revolutionize the treatment of HER2-positive and HER2-Low breast cancer, offering a new era of targeted therapy with improved efficacy and safety.