Background: College dropout has been described as an epidemic, with underrepresented minority (URM) students having the highest dropout rates at colleges and universities. This study examines interpersonal violence and substance use as potential threats to the academic success of URM students. Methods: This study is a secondary data analysis of the National College Health Assessment. Results: Significant decreases for grade point average (GPA) in African American students were associated with physical violence and marijuana use. For Hispanic/Latinx students, physical violence, marijuana use, and methamphetamine use were significantly associated with decreases in GPA. American Indian, Alaska Native, or Native Hawaiian students' decreases in GPA were significantly associated with marijuana use. Conclusions: Results of the study indicated that substance use and interpersonal violence are associated with decreases in GPA for various groups of URM. These findings are disconcerting and relay the importance for colleges and universities to undertake strategies to increase the retention of URM students.