Antibody–drug conjugates (ADCs) are a promising cancer treatment modality that delivers highly cytotoxic payloads to tumors. However, to fully realize their potential, innovative molecular designs are needed to address challenges such as drug resistance, tumor heterogeneity, and treatment-related adverse effects. Emerging ADC formats include bispecific ADCs, conditionally active ADCs (probody–drug conjugates), immune-stimulating ADCs, protein-degrader ADCs, and dual-drug ADCs, each offering unique capabilities. For example, probody–drug conjugates enhance tumor specificity, while bispecific ADCs and dual-drug ADCs address resistance and heterogeneity. The integration of immune-stimulating and protein-degrader ADCs into existing treatment strategies could enable multimodal cancer treatment. Patient stratification and biomarker identification are crucial for identifying patients most likely to benefit from these emerging ADCs. As we continue to deepen our understanding of tumor biology and refine ADC design, we will develop more effective and safe ADCs for treatment-refractory cancers. This review highlights advances in each ADC component and provides detailed discussions on selected examples of emerging novel ADCs.Antibody–drug conjugates (ADCs) are a promising cancer treatment modality that delivers highly cytotoxic payloads to tumors. However, to fully realize their potential, innovative molecular designs are needed to address challenges such as drug resistance, tumor heterogeneity, and treatment-related adverse effects. Emerging ADC formats include bispecific ADCs, conditionally active ADCs (probody–drug conjugates), immune-stimulating ADCs, protein-degrader ADCs, and dual-drug ADCs, each offering unique capabilities. For example, probody–drug conjugates enhance tumor specificity, while bispecific ADCs and dual-drug ADCs address resistance and heterogeneity. The integration of immune-stimulating and protein-degrader ADCs into existing treatment strategies could enable multimodal cancer treatment. Patient stratification and biomarker identification are crucial for identifying patients most likely to benefit from these emerging ADCs. As we continue to deepen our understanding of tumor biology and refine ADC design, we will develop more effective and safe ADCs for treatment-refractory cancers. This review highlights advances in each ADC component and provides detailed discussions on selected examples of emerging novel ADCs.