While the implementation of the first phase 1 trial of a high affinity TEAD inhibitor for adult cancers gives promise that targeting YAP/TEAD therapeutically now has higher potential, results from this review support that a combinatorial approach will be most optimal for YAP-driven heterogeneous tumors, such as neuroblastoma, that carry cooperating alterations that may attenuate single-agent TEAD inhibitor potency. Here, YAP1 is linked to neuroblastoma.