Youth homelessness, a pervasive and persistent problem all over the world, is highly associated with negative behavioral outcomes. Research has found that parental substance use and family conflict were two primary risk factors for youth homelessness, but it remains unclear if absence of family conflicts may lead to different outcomes. While previous research have been exploring the impact of parental absence and parental substance use in the general population, we examined how parental absence and parental substance use, the two main causes of youth homelessness, might impact psychopathology, socio-emotional adjustment, and substance and alcohol abuse and dependence (N = 102, Mean age = 19.3, SD = 0.93). Participants were administered demographic questionnaires, the Weinberger Adjustment Inventory, and the Mini International Neuropsychiatric Interview. Results supported a significant relationship between parental substance use and homeless youth’s depression, p = 0.026, suicidality, p = 0.003, and substance abuse, p = 0.0061 , while parental absence was not significantly correlated with any outcomes. Our findings were consistent with previous research regarding parental substance use, and two potential theoretical frameworks that may explain the routes to youths’ mood disorders and substance use are intergenerational transmission and social cognitive theory.