There is a high overlap between substance misuse and mental health disorders in adolescents. Certain personality traits (i.e., sensation seeking, impulsivity, hopelessness, and anxiety sensitivity) may be related to increased risk for mental health symptoms and/or substance misuse. The current study examined the relationships between personality and both substance use problems and externalizing and internalizing mental health symptoms in two clinical samples of adolescents. One sample consisted of adolescents receiving treatment for a primary mental health disorder, while the other sample included adolescents receiving treatment for a primary substance use disorder. A total of 116 participants (58 for each sample) completed the Substance Use Risk Profile Scale (SURPS), to examine personality factors, the Brief Child and Family Phone Interview- Self-Report, to examine mental health disorder symptoms, and the Personal Experience Screening Questionnaire, to examine substance use problems. After controlling for age, gender, and sample, sensation seeking and impulsivity were positively related to substance use problems, impulsivity was positively related to symptoms of externalizing disorders, and anxiety sensitivity and hopelessness were positively related to symptoms of internalizing disorders. These findings support the utility of the SURPS in predicting theoretically relevant symptoms in clinical samples of adolescents. Moreover, they extend previous research that has focused on using the SURPS as a predictor of substance misuse to its utility in also predicting mental health disorder symptoms. These findings have implications for improving mental health and addictions treatment services for adolescents.