The development of dual-payload antibody-drug conjugates (ADCs) represents a cutting-edge approach to enhancing the therapeutic efficacy of ADCs by targeting multiple pathways simultaneously. By incorporating two distinct cytotoxic agents, dual-payload ADCs have the potential to overcome resistance mechanisms, reduce tumor recurrence, and improve overall treatment outcomes. This strategy leverages the synergistic effects of different payloads to maximize tumor cell kill while minimizing off-target toxicity. This session will explore the challenges and advancements in the design, optimization, and clinical application of dual-payload ADCs, highlighting key considerations such as payload selection, linker design, and safety profiles in clinical development.