In the frame of developing sustainable, reliable, and regenerative interventions on existing buildings, namely on large-scale public housing, the implementation of functional, technological, and effective strategies is devoted to thoroughly assessing the transformability of buildings using trustworthy performance indicators. With this aim, in the present paper, an assessment framework tool is presented and tested to evaluate the potential of buildings for transformation through the detection of regeneration strategies for the reduction of energy consumption, a definition of the new apartments’ internal layout, and the implementation of sustainable systems to foster rainwater harvesting. The procedure is tested on a case study in Latina (Italy), showing its suitability to quantitatively assess the regenerative potentiality of public housing, thus resulting in an effective supporting tool for designers and policy makers.