Entrepreneurial competencies are increasingly essential across all fields and disciplines. However, conventional education frequently inadequately engages non-business students in a setting that demands fostering the development of complex thinking for the multidisciplinary problem-solving increasingly demanded in today’s global landscape. In this sense, this study examines the development of specific skills through a global, challenge-based project involving undergraduate students from different locations and disciplines like engineering, data science, and other non-business backgrounds. Through the Collaborative Online International Learning (COIL) methodology, students in multidisciplinary teams address an entrepreneurial challenge over five weeks by employing machine learning tools to find opportunities and formulate market-oriented solutions. Pre- and post-intervention surveys conducted before and after the intervention assess the influence of cooperation, technology utilization, multicultural involvement, gender, and age on the development of entrepreneurial skills. Regression analyses revealed collaboration as the most influential factor, followed by technology and gender. Results support the integration of international, technology-enhanced, real-world challenges into non-business curricula as a strategy to cultivate entrepreneurial mindsets in technical fields. The findings contribute to the literature on multidisciplinary entrepreneurial education through challenged-based learning projects and provide evidence-based guidance for educators designing global, digitally supported learning.