In an effort to promote integrated STEM education, the Malaysian government has integrated STEM teaching framework within the science and mathematics curriculum specifications to guide the science and mathematics teachers to design and implement interdisciplinary teaching while teaching science and/or mathematics concepts. Some of the factors that make STEM teaching effective include knowledge about integrating the different subjects in teaching and teachers' pedagogical strategies, perceived difficulties (PD), and self-efficacy. This study was designed to measure and model the relationships between these three factors and integrated STEM teaching practices in a sample of Malaysian teachers. Data obtained from 573 science and mathematics teachers were analyzed using a partial least square structural equation modeling approach. Findings revealed that the model derived from a combination of the three factors exhibits substantial predictive power and thus has substantial relevance for STEM teaching. Knowledge and perceived efficacy have significant positive effects on and PD have significant negative direct relationships with STEM teaching. Knowledge has a significant negative and positive mediation effect between difficulties and integrated STEM practices, and self-efficacy and integrated STEM practices, respectively. This study has immediate implications for developing teacher professional development curriculum and STEM education policymakers in Malaysia, and it is a model to be tested in other countries or regions intending STEM education reforms.