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The National Academy of Engineering and NRC Board on Science Education are overseeing a new study of integrated science, technology, engineering, and mathematics (iSTEM) education at the K-12 level. The project aims to develop a strategic research agenda for determining the approaches and conditions most likely to lead to positive outcomes of iSTEM. It will identify and characterize existing approaches to iSTEM education in formal, afterschool, and informal settings; review the evidence for their impact on various parameters of interest, including increasing student awareness, interest, motivation, and achievement in STEM subjects, improving college-readiness skills, and boosting the number and quality of students who may consider a career in a STEM-related field; determine a set of priority research questions to advance understanding of the impacts of iSTEM education; propose methodological approaches for addressing these questions; and identify potential parties who could carry out the research.