Antibodies-drugs conjugate (ADC) are revolutionizing breast cancer treatment thanks to their specific targeting and cytotoxic efficacy. Despite significant advances with agents such as trastuzumab emtansine, sacituzumab govitecan and trastuzumab deruxtecan, resistance mechanisms limit their efficacy. These include reduced or heterogeneous expression of the antigenic target on the surface of tumour cells (HER2, TROP2), mutations in genes encoding the targets of cytotoxic agents, increased efflux of these agents out of the cell, and alterations in intracellular trafficking. These resistances are associated with reduced efficacy of ADCs, underlining the need for new strategies, such as the development of next-generation ADCs by optimizing conjugation systems, for example. Therapeutic prospects also include the development of bispecific antibodies, the targeting of new proteins such as HER3, and the combination of ADCs with other treatments, notably immune checkpoint inhibitors or other ADCs. Despite these advances, challenges remain, notably in identifying biomarkers of response and defining the optimal therapeutic sequence to avoid cross-resistance. Ongoing research is aimed at refining the use of ADCs to maximize their efficacy and prolong the survival of breast cancer patients.