New strategies in antibody-drug conjugates (ADCs), including dual-payload ADCs delivering two distinct cytotoxic agents simultaneously, are gaining momentum to overcome tumor resistance due to heterogeneous antigen expression. These complex constructs face challenges in linker optimization and manufacturing but promise enhanced tumor cell kill by targeting multiple pathways. Additional advances in CAR T cell therapies also show high response rates in lymphomas, reinforcing the momentum in immuno-oncology targeting multiple cancer mechanisms.