The present study was conducted with the aim of proposing and validating an entrepreneurial model to support performance sustainability in the Ministry of Health and Medical Education. This study is applied-developmental in terms of purpose, a cross-sectional survey in terms of data collection method and time frame, and a mixed-methods study in terms of research design. The qualitative sample consisted of entrepreneurship professors and managers from the Ministry of Health and Medical Education, with 20 participants selected through theoretical sampling. Interviews continued until theoretical saturation was reached. The quantitative sample included managers and experts from the Ministry, with a sample size estimated at 140 using Cohen’s power analysis and selected through simple random sampling. Data collection tools included semi-structured interviews and a researcher-made questionnaire. The validity of the interviews was confirmed based on four criteria: credibility, transferability, confirmability, and dependability. The reliability of the qualitative section was assessed using the Holsti coefficient, which yielded a satisfactory value of 0.712. The validity of the quantitative section was evaluated using face validity (expert judgment), convergent validity (above 0.5), and discriminant validity. The reliability of the questionnaire was assessed via Cronbach’s alpha, rho coefficient, and composite reliability, all of which were found satisfactory (above 0.7). Data analysis in the qualitative phase was performed using thematic analysis, and in the quantitative phase using partial least squares (PLS). The results indicated that environmental factors, technological opportunities, entrepreneurial traits, and entrepreneurial infrastructure influence entrepreneurial strategy. In turn, entrepreneurial strategy affects entrepreneurial alertness and entrepreneurial knowledge, which subsequently lead to entrepreneurship in the health, treatment, and medical education sectors. Ultimately, entrepreneurship in this domain results in social, economic, and environmental performance outcomes.