BACKGROUND: While advances in medical and surgical management have allowed >97% of congenital heart disease (CHD) patients to reach adulthood, a growing number are presenting with non-cardiovascular malignancies. Indeed, adults with CHD are reported to face a 20% increase in cancer risk, relative to others, and cancer has become the fourth leading cause of death among this population. Surgical resection remains a mainstay in management of thoracoabdominal cancers. However, outcomes following cancer resection among these patients have not been well established. Thus, we sought to characterize clinical and financial outcomes following major cancer resections among adult CHD patients. METHODS: The 2012-2020 National Inpatient Sample was queried for all adults (CHD or non-CHD) undergoing lobectomy, esophagectomy, gastrectomy, pancreatectomy, hepatectomy, or colectomy for cancer. To adjust for intergroup differences in baseline characteristics, entropy balancing was applied to generate balanced patient groups. Multivariable models were constructed to assess outcomes of interest. RESULTS: Of 905,830 patients undergoing cancer resection, 1,480 (0.2%) had concomitant CHD. The overall prevalence of such patients increased from <0.1% in 2012 to 0.3% in 2012 (P for trend<0.001). Following risk adjustment, CHD was linked with greater in-hospital mortality (AOR 2.00, 95%CI 1.06-3.76), as well as a notable increase in odds of stroke (AOR 8.94, 95%CI 4.54-17.60), but no statistically significant difference in cardiac (AOR 1.33, 95%CI 0.69-2.59) or renal complications (AOR 1.35, 95%CI 0.92-1.97). Further, CHD was associated with a +2.39 day incremental increase in duration of hospitalization (95%CI +1.04-3.74) and a +$11,760 per-patient increase in hospitalization expenditures (95%CI +$4,160-19,360). CONCLUSIONS: While a growing number of patients with CHD are undergoing cancer resection, they demonstrate inferior clinical and financial outcomes, relative to others. Novel screening, risk stratification, and perioperative management guidelines are needed for these patients to provide evidence-based recommendations for this complex and unique cohort.