Recently, the National Institute of Mental Health (NIMH) introduced the Research Domain Criteria (RDoC) initiative to address two major challenges facing the field of psychiatry: (1) the lack of new effective personalized treatments for psychiatric disorders, and (2) the limitations associated with categorically defined psychiatric disorders. Although the potential of RDoC to revolutionize personalized psychiatric medicine and psychiatric nosology has been acknowledged, it is unclear how to implement RDoC in naturalistic clinical settings as part of routine outcomes research. In this article, the authors present the major RDoC principles and then show how these principles are operationalized in The Menninger Clinic's McNair Initiative for Neuroscience Discovery-Menninger & Baylor College of Medicine (MIND-MB) study. The authors discuss how RDoC-informed outcomes-based assessment in clinical settings can transform personalized clinical care through multimodal treatments.