Universities’ entrepreneurship and innovative practices are burgeoning all over Italy. Some of these practices resonate at the international level while others have a local impact. Italian higher education faces some important challenges and actions need to be taken to unleash its full potential. Promoting the entrepreneurial and innovation agenda can help Italy improve the overall performance of the higher education system, and of individual universities, in all regions. The government has started providing a strategic support to engagement, which could catalyse Italy’s innovation capacity, human capital endowment, and well-being. This review illustrates policy actions promoting the entrepreneurial and innovative activities in the Italian Higher Education System, and focuses on 11 case study universities. It discusses strategies and practices adopted by Italian higher education institutions to innovate, engage, and generate value for the society and the economy. This review is part of a series of national reports implementing the HEinnovate framework. HEinnovate is a guiding framework that the OECD and the European Commission have developed to promote the “entrepreneurial and innovation agenda” in higher education.