Contemporary needs in terms of sustainability, energy production/consumption and smart management of our cities have to face and give concrete answers – as adequate methodologies and technologies - to the problem of the interventions on listed historical architectures and Cultural Districts. These, infact, are under protection of local, national or international Institutions that are often far from really understanding and controlling the issues of management and energy efficiency improvement. This is the main objective of the research here presented, focused on a huge historical complex in the heart of the city of Genoa, now largely abandoned and party already reused as humanistic university pole. The feasibility study for its complete reuse and restoration contains a part focused on its smart management: enhancement of its thermal behaviour compatibly with its architectural and historical values, energy production recurring to renewable sources, enhancement of its ‘energy’ management within a Cultural District framework.