The shortage of graduates in Science, Technology, Engineering and Mathematics (STEM), has led to numerous attempts to increase students’ interest in STEM. One emerging approach that has the potential to improve students’ motivation for STEM is integrated STEM education. Nonetheless, the implementation of this new instructional strategy is not straightforward due to the lack of consensus about instructional practices in integrated STEM. This paper contributes to this challenge by providing a well-defined framework for instructional practices in integrated STEM in secondary education, based on the results of a systematic review of existing literature. The framework contains five key principles: integration of STEM content, problem-centered learning, inquiry-based learning, design-based learning and cooperative learning. The proposed framework has several benefits, including its applicability in the classroom and the possibility to describe integrated STEM on multiple dimensions. Nonetheless, further research is necessary to investigate the effects of integrated STEM on students’ cognitive and affective learning outcomes.