Children with congenital heart disease (CHD) have elevated neuroblastoma (NB) risk, potentially due to shared neural crest origins. We analyzed rare exonic de novo single-nucleotide variants in 702 CHD and 454 NB trios from the Neuroblastoma Epidemiology in North America Study, Gabriella Miller Kids First Program, and a published cohort. Seven genes, including CHD risk genes POGZ and LZTR1 (linked to Noonan syndrome and Schwannomatosis), showed nominal (p < 0.05) enrichment in both cohorts. CIC, IREB2, POGZ, and PCDHG cluster are associated with neurodevelopmental disorders, supporting shared developmental mechanisms. Findings warrant investigation of pathways linking congenital anomalies and childhood cancer.