This paper explores the entrepreneurial activities and models of Science & Technology universities. Employing a mixed-method design with a questionnaire and semi-structured interviews we find three main entrepreneurial models based on different configuration of activities and different organizational and regional characteristics: (1) an “engage” model, which focuses on local economic development (2) a “formal” model, which focuses on the financial advantage of universities and their faculties and (3) a “comprehensive” model, which focuses on the local economic development and the financial advantage of universities and their faculties. This paper extends previous literature by encompassing the conventional distinction between formal and informal entrepreneurial activities. It also contributes to the emerging literature on entrepreneurial university models and the strategic approaches by identifying the different models of entrepreneurial universities in the European setting of S&T universities focusing on the role played by organizational and ecosystem factors in affecting the adoption of a specific model by universities.