This study examined the genetic and environmental architecture of early gambling involvement and substance use to determine whether genetic or environmental factors that contribute to substance use also put young adolescents at risk for early involvement in gambling. Self-reports of substance use and gambling involvement were collected at age 13 years from 279 Monozygotic and Dizygotic twin pairs. Univariate ACE modeling revealed that genetic and nonshared environmental factors almost equally accounted for gambling involvement, with no contribution from shared environmental factors. In contrast, both shared and nonshared environmental factors played important roles in substance use; the contribution of genetic factors was also substantial. Bivariate analyses identified a significant, albeit modest, overlap between the genetic influence on gambling involvement and the genetic influence on substance use. The results shed light on the etiology of early gambling involvement and substance use, suggesting that preventive interventions targeting common risk factors may also need to be complemented by modules that are specific to each behavior.