A promising approach to increase students' motivation for science, technology, engineering, and mathematics (STEM) is integrated STEM education (iSTEM). This is an instructional approach that emphasizes the deeper connections between the STEM disciplines by involving students in design challenges centered around real-world problems. However, the successful implementation of a new instructional approach, such as iSTEM, strongly depends on teachers' attitudes toward the innovation. Therefore, a deeper understanding of teachers' attitudes toward teaching iSTEM is necessary. This study uses a survey method to investigate the influence of teachers' background characteristics and school context variables on teachers' attitudes toward teaching iSTEM. To do so, a differential approach is used. Attitudes toward five key principles for iSTEM (integration, problem-centered, inquiry-based, design-based, and cooperative learning) are examined separately to get a more in-depth and nuanced insight into the factors influencing these attitudes. Results of the multiple regression analyses show that participation in professional development is positively linked to teachers' attitudes toward all key principles, whereas several other teacher and school context variables are positively correlated with attitudes toward one or two principles. Moreover, experience in mathematics and total years of teaching show a negative correlation with several aspects of teachers' attitudes toward teaching iSTEM. Findings of this study are valuable, since they not only provide insight into possible barriers to the implementation of iSTEM but also suggest opportunities for overcoming these barriers.