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Abstract This paper describes a decolonial perspective on material agency in the context of STEM education and application. Using the framework of generative STEM, we engaged in case studies with African, African American, South American, and Native American educational communities. This research shows that understanding material agency based on Indigenous knowledge systems can open a rich source of research and education content. Using a suite of simulations, Culturally Situated Design Tools, we apply this body of research to the classroom. One important theoretical conclusion is the contrast to a “content agnostic” position. A generative framework instead offers a robust blend of user agency and instructional guidance. The outcomes indicate statistically significant and notable improvement for STEM skills and interests. We conclude with a contrast to the quantum epistemology approach to posthumanism. We show that the Indigenous material agency framework in generative STEM is a better fit to decolonial aspirations, and that it offers a more transformative vision for the potential role of STEM in transitioning from an extractive to a generative economy.