There is an urgent need to increase the environmental, economic, and social sustainability of buildings. Indeed, construction has one of the lowest rates of sustainability among productive sectors, associated with high energy demand and pollutant emissions, frequent cost increase and time delays, and poor and unsafe working conditions. Building prefabrication is a construction technique that can enhance the sustainability of buildings, in terms of predictability, product and process quality, and increased safety for workers. Recently, new approaches and concepts such as Industry 4.0 (Construction 4.0) and circularity of resources emerged in the field of prefabrication to potentiate the benefits of off-site construction. In this scenario, the scope of the work is to analyze the state of the art in the field of prefabricated building technologies in the light of these innovations and to evaluate their performances from a sustainability perspective. The work has been developed in two phases: (1) analysis of 13 case studies of prefabricated technologies in Europe; (2) comparative assessment of their sustainability performances according to 21 qualitative parameters. Based on the results of the work, a set of guidelines is proposed as the outcome, i.e., suggested strategies and approaches for designers and industry professionals that can be used to enhance the sustainability of prefabrication.