AbstractAnswering questions and solving problems are critical skills that affect the quality of life for all people. The content areas of science and engineering traditionally and most directly address the processes of inquiry and problem‐solving. While there is an increasing body of research surrounding teaching academic content (i.e., mathematics and science) as well as skills that are critical to support student success in these areas (i.e., communication and self‐determination), the research supporting instruction of math, science, and engineering practices and processes are only emerging. The purpose of this article is to provide a research‐based framework for instructional design that provides ideas for cognitive accessibility and supports for students with MSD in STEM. The framework aims to guide teachers in considering why to teach STEM, what to teach, and how to teach it. The framework guides teachers to use evidence‐based practices in special education to teach students to know about STEM (i.e., academic content), do STEM practices and processes (i.e., critical thinking skills combined into routines for asking questions or solving problems), and think in ways that support this learning (i.e., metacognitive behaviors).