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Behavior genetic methods are useful for examining mechanisms underlying the interaction between genetic and family environmental factors of internalizing problem behavior (INT). Previous twin studies, however, have shown little consistency in interaction patterns, depending on type and operationalization of measured environments. The aim of the current study was to explore different gene-by-environment interaction patterns among different family-level environmental risk factors and resources known to correlate with INT. Using an empirical-based approach, we combined various indicators of the family environment to derive four dimensions: positive parenting, negative parenting, lack of parental resources, and socioeconomic status. We then used a genetically informed design of twins raised in the same family to test whether interaction patterns followed a diathesis stress or vantage sensitivity model formulation. The sample consisted of 2,089 twin pairs and their families from two twin birth cohorts (ages 11 and 17) participating in Wave 1 of the German TwinLife study of social inequalities. In line with a vantage sensitivity pattern of interaction and with the bioecological model of development (Bronfenbrenner & Ceci, 1994), evidence for a general mechanism of gene–environment interaction with increasing nonshared environmental variance for more adverse and less propitious family conditions was found. In preadolescence, parenting behavior had a greater moderating influence on INT compared to general family conditions like socioeconomic status. Interventions for INT that directly involve parents, thus, may be more important in preadolescent populations whereas individual interventions for adolescents may be more successful if they are adapted to different levels of socioeconomic status. Public Significance Statement: The present study suggests that environmental influences outside the family may have a greater impact on internalizing problem behavior under less advantageous family conditions. In preadolescence, interventions for internalizing problem behavior should involve parents directly whereas in adolescence, interventions may be tailored individually that take into account adolescents' socioeconomic status. [ABSTRACT FROM AUTHOR]