The University System as a whole is called upon today to play a leading role in the transition towards the so-called Society 5.0, a society capable of placing citizens at the center and of using knowledge, innovation and technology to respond to changing social needs. But is the Italian University today in a position to play this proactive and irreplaceable role for the country? What does the Italian University System need to unravel the knots that today limit its attractiveness and effectiveness? Ambrosetti Club launched, in November 2019, a research and reflection process that involved the main stakeholders of the Italian university world, engaging them in a dialogue with business leaders and national and international experts, to identify the problems to be solved and the 10 proposals to be implemented to achieve a real University 5.0 in Italy.