Objectives: Many medical students experience career decision-making stress in the final phase of training. Yet, the factors that induce or reduce career decision-making stress and how progression in their clerkships relates to these factors are unknown. This knowledge gap limits the possibilities for medical schools to develop and implement interventions targeting students’ career decision-making stress. This study explores content, process, and context factors that may affect career decision-making stress. Methods: Using cross-sectional survey data from medical master students (n = 507), we assessed content (future work self), process (choice irreversibility, time pressure, career decision-making self-efficacy), and context (supervisory support, medical school support, study load, competition) factors and their relationships with career decision-making stress. The hypothesized relationships were tested with structural equation modelling. Results: A clearer future work self and higher career decision self-efficacy were associated with lower career decision-making stress, while experienced time pressure, competition, and study load were associated with higher career decision-making stress. Choice-irreversibility beliefs, supervisory support, and medical school support were unrelated to career decision-making stress. As students’ clerkships progressed, they gained a clearer future work self, but also experienced more time pressure. Discussion: Clinical clerkships help students to form a clearer future work self, which can diminish career decision-making stress. Yet, students also experience more time pressure as the period of clerkships lengthens, which can increase career decision-making stress. A school climate of high competition and study load seems to foster career decision-making stress, while school support hardly seems effective in diminishing this stress.