Abstract Allostatic load (AL) is the cumulative ‘wear and tear’ on the body due to chronic adversity. We tested the poly-environmental (exposomic) and polygenic contributions to AL and their combined contribution to adolescent mental health. In this cohort study of N = 5,036 diverse youth (mean age 12 years) from the Adolescent Brain Cognitive Development Study, we calculated a latent AL score, childhood exposomic risk and genetic risk.