Substance use and misuse among college students has presented unique challenges for institutions of higher education. As such, this three-article dissertation sought to examine and explore antecedent factors, such as student demographics, protective behavior strategies, mental health, academic performance, and how they interact with alcohol consumption, including heavy episodic drinking. Using the 2015 – 2019 American College Health Association – National College Health Assessment II (ACHA-NCHA II) data cohorts, the first article examined the factor structure of the items assessing protective behavioral strategies and mental health through exploratory factor analysis using principle component analysis. Building upon the first article, the second article used the factor solution found in the previous article to include in structural equation model analyses to assess the indirect and direct effects of the predictor variables of interest on academic performance. Moving from the empirical articles, the third article focused on a higher education practitioner’s perspective of the current status of collegiate recovery centers and how results from analyses in the previous two articles inform how higher education professionals and administrators should combat the increasingly alarming issues with substance use prevalent among college students. This three-article dissertation concluded with discussions on future directions for research as well as implications and recommendations for practitioners and policy in institutions of higher education.