The "leaky pipeline" with regard to students' engagement in Science, Technology, Engineering, and Mathematics (STEM) has triggered extensive research to understand and prevent students dropping out from STEM. To boost enrolment and interest in STEM fields, integrated STEM (iSTEM) education could be harnessed by providing students with relevant challenges. This study investigated (1) the evolution of affective outcomes regarding science and mathematics over time in traditional education, (2) the impact of an iSTEM curriculum on affective outcomes with regard to science and mathematics, and (3) the differential effectiveness of the iSTEM curriculum regarding student characteristics. Therefore, an iSTEM intervention was developed and evaluated over the course of 2 years. In total, 859 grade 9 students, distributed across 39 different Belgian schools, participated in the longitudinal study. The results of multilevel analyses show that students' attitudes, motivation, and self-efficacy with regard to science and mathematics tend to become less positive over time in traditional education. On the other hand, iSTEM education had positive effects on attitudes towards science and mathematics. However, negative results were observed with regard to motivation and self-efficacy outcomes. In addition, intervention effects differed for boys and girls and for students at different socioeconomic status levels. Our results indicate that iSTEM has the potential to improve students' attitudes towards STEM, but that we should be careful with regard to the implementation of this approach in terms of student motivation and self-efficacy.