Research on the mental health needs of maltreated youth in out-of-home care remains limited. The goal of the current study was to examine two common mental health concerns (i.e., depression, substance use) among 122 12-15 year olds in out-of-home placements. Specifically, we investigated potential risk and protective factors among socio-demographic, maltreatment, youth, family, and community variables. We relied on data collected through the AAR-C2, a Canadian needs assessment and outcome monitoring tool. Approximately 4 in 10 (39.2%) youth endorsed at least one mental health problem, which we defined as the youth scoring at least one standard deviation above the sample mean for the depression items and the youth indicating the presence of alcohol and/or substance use over the past year. Almost 1 in 10 (8.3%) reported struggling with both mental health issues. Results from logistic regressions indicated that adolescent females were at higher risk of experiencing depression than males, and increasing age was associated with increased risk for substance use. Turning to protective factors, results indicated that the greater the perceived quality of the youth-caregiver relationship, the lower the risk for mental health difficulties (i.e., depression, substance use). Moreover, participation in extracurricular activities appeared to protect youth against depression or substance use. Results imply that the youth-caregiver relationship and involvement in extracurricular activities are important areas to consider to promote the well-being of maltreated youth in out-of-home care.