The present experiment was designed to determine whether individual variation in neurobiological mechanisms associated with substance abuse risk moderated effects of a brief preventive intervention on social competency skills. This study was conducted in collaboration with the ongoing preventive intervention study at Johns Hopkins University Prevention Intervention Research Center (JHU PIRC) within the Baltimore City Public Schools. A subsample (N = 120) of male 9th grade students was recruited from the larger JHU study population. Approximately half of the participants had a current or lifetime diagnosis of CD while the other half had no diagnosis of CD or other reported problem behaviors. Measures of executive cognitive function (ECF), emotional perception and intelligence were administered. In a later session, participants were randomly assigned to either an experimental or control group. The experimental group underwent a facilitated session using excerpted materials from a model preventive intervention, Positive Adolescent Choices Training (PACT), and controls received no intervention. Outcomes (i.e., social competency skills) were assessed using virtual reality vignettes involving behavioral choices as well as three social cognition questionnaires. Poor cognitive and emotional performance and a diagnosis of CD predicted less favorable change in social competency skills in response to the prevention curriculum. This study provides evidence for the moderating effects of neurocognitive and emotional regulatory functions on ability of urban male youth to respond to preventive intervention materials.