Changes in contemporary age force the scientific community to face the challenges of sustainability also within the historical context. It is not just a purely investigation on ecological footprint or energy efficiency; it is a crucial issue for human activity and behaviour. The article presents the new horizon of research opened within the work of a multidisciplinary group on the complex of the Albergo dei Poveri of Genoa, in order to facilitate its complete re-use as humanistic didactic university pole. The research is finalised to set up a knowledge system to improve the management process of any future intervention on the complex, touching the four pillars of sustainability: economics, environmental, social and cultural, beyond the purely technical and energetic sphere. Main objective is also to reach more general results, touching also the methodological sphere.