International students outperform U.S. students in science, technology, engineering, and mathematics (STEM), while U.S. students increasingly leave these high-demand areas. To improve STEM education, it is imperative to determine the most effective and efficient instructional and organizational practices in these courses. This article identifies evidence-based strategies through the combination of a case study and a research review. The identified best practices fell within three clusters: (a) structuring a course, (b) focusing on how to teach, and (c) assessing student performance. Examples from a case study in a large introductory biology classroom are highlighted as each cluster is empirically examined.