Purpose <p>Research Experience for Undergraduates (REUs) programs are valuable opportunities for biomedical engineering (BME) students to gain hands-on laboratory experience. However, as part of these REU programs, BME students rarely have direct contact with industrial settings, potentially limiting the impact these programs can have for roles outside of academia. To address this gap, an REU program was developed that helped students work with mentors from industry start-ups and engage in specially designed professional development modules. This study examines the modules, provided to the REU students as “challenges,” that were designed to foster an entrepreneurial mindset (EM) and accelerate students’ research impact.</p> Methods <p>Undergraduate students participated in REU programs at three institutions and were assigned faculty or start-up company mentors. Students were asked to complete at least eight of the ten professional development and EM challenges, submitting reflections after each challenge. These reflections were deductively analyzed using a conceptual framework of learning outcomes related to EM.</p> Results <p>Analysis of reflections showed developmental value in completing the challenges. Furthermore, although the challenges were designed to support certain EM outcomes, the students’ reflections demonstrated other EM characteristics beyond what was anticipated based on the challenges’ designs.</p> Conclusions <p>Overall, this study demonstrates the utility of integrating professional development modules into students’ research programs that target skills necessary within and outside academia. Additionally, it has been shown that these challenges can assist with students’ EM development. Given the student-selected nature of the challenges, they can be implemented to strengthen the research experience for students across various settings.</p>