In the United States, less than half of the students who enter into science, technology, engineering, and mathematics (STEM) undergraduate curricula as freshmen will actually graduate with a STEM degree. There is even greater disparity in the national STEM graduation rates of students from underrepresented groups with approximately three-fourths of minority students leaving STEM disciplines at the undergraduate level. A host of programs have been designed and implemented to model best practices in retaining students in STEM disciplines. The Howard Hughes Medical Institute (HHMI) Professors Program at Louisiana State University, under leadership of HHMI Professor Isiah M. Warner, represents one of these programs and reports on a mentoring model that addresses the key factors that impact STEM student attrition at the undergraduate level. By integrating mentoring and strategic academic interventions into a structured research program, an innovative model has been developed to guide STEM undergraduate majors in adopting the metacognitive strategies that allow them to excel in their programs of study, as they learn to appreciate and understand science more completely. Comparisons of the persistence of participants and nonparticipants in STEM curricular, at the host university and with other national universities and colleges, show the impact of the model's salient features on improving STEM retention through graduation for all students, particularly those from underrepresented groups.