This article describes a framework for how to provide more accessible, relevant, and effective instruction in science, technology, engineering, and mathematics (STEM) education to all students. The STEM for All initiative asserts that all students, including those with disabilities and other diverse learning needs, should be included in meaningful STEM education and develop expertise in STEM areas as well as 21st century skills associated with STEM learning. This framework is described through the lens of Bronfrenbrenner's (1977, 1994) ecological model, which provides a mechanism for understanding the interconnected and complex interactions that occur across multiple systems (e.g., policy makers, curriculum developers, teachers, and students) within the current STEM education infrastructures. Examples and lessons learned from the Furthering Urban STEM Innovation, Outreach, & New Research (UC|FUSION) research and outreach STEM center illustrate how the model is currently applied in Ohio schools and how it could be adapted to other local, regional, and national STEM FOR ALL initiatives.