Many researchers consider a lacking interest in science and the students' belief that science is too demanding as major reasons why young people do not strive for science-related careers. In this article, we first delineated a theoretical framework to investigate the importance of interest, self-concept, and school factors regarding students' career preferences. Then, we tested the expected effects on a sample of German 9th-grade students ("N" = 7,813). We focused on two school factors: the amount of (additional) science activities and the real-life applications in science classes. The multi-level analysis showed that school factors were highly relevant for the students' interest in science and science self-concept. In turn, interest in science and science self-concept affect the students' interest in science-related careers. We conclude that focusing on the link between individual and school characteristics is important for the understanding of students' interest in science-related careers.