Background: In responding to the global problems facing humankind, there is great value in equipping science and engineering students with skills to function well in multidisciplinary teams. Little attention has been paid into the factors that influence multidisciplinary collaboration and teamwork of science and engineering students. Purpose: This research describes multidisciplinary teamwork of applied physics and mechanical engineering students in a challenge-based learning (CBL) course. The study aimed to: a) identify the facilitators and barriers to multidisciplinary teamwork and b) explore learning outcomes connected to working in multidisciplinary teams. Sample: 30 students registered to the course, two teachers, and three tutors participated in this research. Design and Methods: An instrumental case study was conducted in the context of a pilot CBL course. Data included interviews, reflection reports, observations, and design posters. Transcribed video recordings were searched in an attempt to demonstrate the codes revealed with the qualitative content analysis of interview transcripts and reflection reports. Results: The results indicated knowledge acquisition, application, and an awareness of other disciplinary approaches as the learning outcomes with some differences for engineering and physics students. The findings also yielded individual (e.g. knowledge of control theory), team (e.g. disciplinary perspectives), and course factors (e.g. disciplinary connections to the challenge) that influenced multidisciplinary teamwork. Conclusion: Multidisciplinary teamwork is supported by the unique ways of thinking and approaching problems of the two disciplines. Implications contribute to future research and thinking for similar learning environments while improving student learning in multidisciplinary teams.