Antibody - drug conjugates（ADC），as a class of innovative therapies，have shown significant activity in breast cancer. ADCs are conjugated from monoclonal antibodies，linkers and cytotoxic payloads，which harnesses the highly specific targeting capabilities of antibodies along with the potent cancer killing effects of the cytotoxic drugs，demonstrating significant efficacy in the treatment of breast cancer. Nonetheless，as ADCs have been widely used in clinical practice，resistance to ADCs has been observed in breast cancer patients. In this review，we summarized ADCs’current applications in the treatment of breast cancer and classified the mechanisms underlying ADC resistance into several distinct categories as follows：inadequate antigen - antibody binding，impaired internalization and trafficking pathways of ADCs，defective lysosomal function，aberrant payload release，tumor insensitivity to the payloads，and cyclin deficiency. Furthermore，we summarized the contemporary strategies designed to address ADC resistance，such as the combined use of ADCs with other therapeutic agents，including chemotherapeutic agents，targeted therapies，and immune checkpoint inhibitors，as well as the development of new drugs. This review aims to offer reference options for the treatment of patients with ADC-resistant breast cancer.