Understanding the degree to which students’ interests and achievement fit with educational environmental rewards and requirements can help universities retain students, while assisting students in finding fulfilling academic majors and careers. We examined the effect of various interest-major congruence indices and American College Testing (ACT) achievement indicators on biology and chemistry students’ success and retention using archival university data from a Historically Black College/University. Results indicated that the specific congruence index utilized alters the statistical impact of achievement indicators on retention and success. Additionally, while the predictors of success and retention differed between biology and chemistry majors, math and English ACT scores impacted success and retention for both biology and chemistry majors, highlighting the utility of assessing skill areas beyond math for students majoring in both biology and chemistry. Career counselors and advisors should consider students’ majors and the utility of exploration tools when providing guidance to college students.