The current study longitudinally examines the effects of child maltreatment, parenting, and disadvantaged neighborhood on victimization, delinquency, and well-being via running away and school engagement among a sample of 360 high-risk adolescents. Results of a path analysis revealed that parenting was associated with school engagement, running away, and well-being. Childhood neglect was related to victimization while sexual abuse and living in a more disadvantaged neighborhood were associated with poorer well-being. Greater school engagement was associated with higher levels of well-being and a lower likelihood of delinquency. Finally, running away was positively associated with participating in delinquent activities. In terms of the interactions, results showed that the effect of positive parenting on well-being was significantly stronger for females and the manner in which neglect related to school engagement was greater among males. Additionally, gender significantly moderated the relationship between running away and victimization and between running away and delinquency, both of which the effects were significantly stronger for males. Implications for families and adolescents are addressed.