Overall, we demonstrate that dual inhibition of CDK9 and CDK2 attacks MYCN dependence in NB through several mechanisms, including (a) selective blockade of CDK9 and superenhancer-regulated nascent endogenous MYCN transcription; (b) induction of CDK9/2-mediated proapoptotic pathways; and (c) selective targeting of MYCN-regulated adrenergic gene expression in NB. Here, CDK9 is linked to neuroblastoma.