Objective: Risky substance use among college students is widespread, and associated with numerous adverse consequences. Current interventions focus primarily on students' current substance use; we hypothesize that shifting focus from current use to underlying risk factors is a complementary approach that may improve effectiveness of prevention/intervention programming. This approach aligns with the personalized medicine movement, which aims to harness knowledge about underlying etiological factors to provide individuals with specific information about their unique risk profiles and personalized recommendations, to motivate and enable individuals to better self-regulate their health. Method: Our group is building and evaluating an online Personalized Feedback Program (PFP) for college students that provides feedback about the individual's underlying genetically influenced externalizing and internalizing risk factors for substance use, along with personalized recommendations/resources. The project capitalizes on work from a university-wide research project (Spit for Science; S4S), in which > 12,000 students (˜70% of 5 years of incoming freshmen) are being followed longitudinally to assess substance use and related factors across the college years. In this article, we describe our foundational work to develop the PFP. Results: From the S4S data, we have identified risk factors across four domains (Sensation Seeking, Impulsivity, Extraversion, and Neuroticism) that are correlated with college students' substance use. We developed an online self-guided PFP, in collaboration with professionals from student affairs, and using feedback from students, with the ultimate goal of conducting a randomized clinical trial. Conclusion: The provision of personalized risk information represents a novel approach to complement and extend existing college substance use programming. (PsycInfo Database Record (c) 2022 APA, all rights reserved).