This review discusses the clinical efficacy and safety of Food and Drug Administration (FDA)-approved antibody–drug conjugates (ADCs) in treating human cancers. ADCs, which combine monoclonal antibodies with cytotoxic drugs, offer improved target specificity and reduced toxicity compared to traditional chemotherapy. Currently, 13 FDA-approved ADCs are available, and over 100 are in clinical trials. The review highlights the mechanisms, efficacy, and safety profiles of several key ADCs, including gemtuzumab ozogamicin (GO), brentuximab vedotin (BV), trastuzumab emtansine (T-DM1), inotuzumab ozogamicin (InO), moxetumomab pasudotox (MP), polatuzumab vedotin (PV), enfortumab vedotin (EV), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), disitamab vedotin (RC48), loncastuximab tesirine (LT), tisotumab vedotin (TV), and mirvetuximab soravtansin (MIRV). Each ADC is evaluated based on its target, mechanism of action, and clinical outcomes, with a focus on overall survival, progression-free survival, and safety profiles. The review also discusses the challenges and future perspectives in ADC development, emphasizing the need for improved targeting, reduced toxicity, and enhanced stability. Despite ongoing advancements, optimizing ADCs to maximize efficacy and minimize side effects remains a critical area of research.This review discusses the clinical efficacy and safety of Food and Drug Administration (FDA)-approved antibody–drug conjugates (ADCs) in treating human cancers. ADCs, which combine monoclonal antibodies with cytotoxic drugs, offer improved target specificity and reduced toxicity compared to traditional chemotherapy. Currently, 13 FDA-approved ADCs are available, and over 100 are in clinical trials. The review highlights the mechanisms, efficacy, and safety profiles of several key ADCs, including gemtuzumab ozogamicin (GO), brentuximab vedotin (BV), trastuzumab emtansine (T-DM1), inotuzumab ozogamicin (InO), moxetumomab pasudotox (MP), polatuzumab vedotin (PV), enfortumab vedotin (EV), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), disitamab vedotin (RC48), loncastuximab tesirine (LT), tisotumab vedotin (TV), and mirvetuximab soravtansin (MIRV). Each ADC is evaluated based on its target, mechanism of action, and clinical outcomes, with a focus on overall survival, progression-free survival, and safety profiles. The review also discusses the challenges and future perspectives in ADC development, emphasizing the need for improved targeting, reduced toxicity, and enhanced stability. Despite ongoing advancements, optimizing ADCs to maximize efficacy and minimize side effects remains a critical area of research.