The MHEO Fifth Report covers the foundational topic of the socio-economic impact and sustainability of the Italian system of higher education, with an interdisciplinary approach. After a first Section presenting trends and dynamics of higher education in the world, in Italy, in Lombardy and in Milan, the second Section of the Report presents in-deep analyses on university patents and spin-offs, civic universities, and a survey on students’ financial knowledge. The third Section examines the environmental, social and economic-financial bases of the Italian higher education system, with a special focus on the public financing of universities through the Ordinary Financing Fund. The Report closes with an appraisal of the last three years of activities promoted by MHEO.