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Adult survivors of childhood cancer have high rates of obesity, which in combination with the cardiotoxic effects of specific cancer therapies places them at high-risk for cardiovascular morbidity. Here we show the contribution of genetic risk scores to increase prediction of those childhood cancer survivors at risk for severe obesity (Body Mass Index ≥40 kg/m(2)) as an adult. Among 2,548 five-year survivors of European ancestry from the St. Jude Lifetime Cohort Study, the genetic risk score was found to be associated with 53-fold higher odds of severe obesity. Addition of genetic risk scores to risk prediction models based on cancer-treatment exposures and lifestyle factors, significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in identification of 4.3-times more high-risk survivors), which was independently validated in 6,064 survivors from the Childhood Cancer Survivor Study. Genetic predictors improve identification of patients who could benefit from heightened surveillance and interventions to mitigate the risk of severe obesity and associated cardiometabolic complications.