Antibody-drug conjugates have emerged as a promising cancer treatment, combining targeted delivery of cytotoxic agents with the specificity of monoclonal antibodies. Despite their potential, ADCs face limitations such as resistance and off-target effects. To enhance their efficacy, ADCs are increasingly being combined with other therapeutic strategies, including immune checkpoint inhibitors, chemotherapy, small-molecule inhibitors, anti-angiogenic agents, and CAR-T cell therapies. These combination therapies aim to overcome resistance mechanisms, improve tumor targeting, and boost immune responses. Clinical studies have shown that such combinations can significantly improve response rates and progression-free survival across various cancers. This review explores the mechanisms, clinical efficacy, key studies, challenges, and future perspectives of Antibody-drug conjugates combinations in cancer therapy.