Problem-solving has been one of the major strands in science education research. But much of the problem-solving research has been conducted on discipline-based contexts; little research has been done on how students, especially individuals, solve interdisciplinary problems. To understand how individuals reason about interdisciplinary problems, we conducted an interview study with 16 graduate students coming from a variety of disciplinary backgrounds. During the interviews, we asked participants to solve two interdisciplinary science problems on the topic of osmosis. We investigated participants' problem reasoning processes and probed in their attitudes toward general interdisciplinary approach and specific interdisciplinary problems. Through a careful inductive content analysis of their responses, we studied how disciplinary, cognitive, and affective factors influenced their interdisciplinary problems-solving. We found that participants' prior discipline-based science learning experiences had both positive and negative influences on their interdisciplinary problem-solving. These influences were embodied in their conceptualization of the interdisciplinary problems, the strategies they used to integrate different disciplinary knowledge, and the attitudes they had toward interdisciplinary approach in general and specific interdisciplinary problems. This study sheds light on interdisciplinary science education by revealing the complex relationship between disciplinary learning and interdisciplinary problem-solving.