This chapter systematically explores the design of an innovative entrepreneurship course and its redesign through several iterations over a 7-year period, following a data-driven Design Science Research (DSR) approach. It offers a case study of the “innovation Space Project: Innovation and Entrepreneurship Processes (ISP)” course at the Eindhoven University of Technology. The course uses a Challenge-Based Learning (CBL) approach, engaging students in interdisciplinary teams and tackling open-ended challenges in collaboration with societal stakeholders. We analyse the evolution of the course through the lens of constructive alignment, providing insights into the design decisions that have facilitated its continuous improvement over the years. A longitudinal comparative analysis was conducted to map the changes in learning objectives, activities, and assessment methods. Data-driven DSR prioritises ongoing data collection and analysis as a core component of the educational design process. This involves not just traditional academic performance data but also qualitative feedback from students, reflections from educators, and input from industry and societal stakeholders. This case study contributes to the empirical body of entrepreneurial education knowledge and serves as a model for applying data-driven DSR principles in educational research and practice.