We previously identified that urban brownfield regeneration projects are relevant strategies to limit urban sprawl while revitalizing portions of cities, namely mixed-use neighbourhoods. Moreover, these neighbourhoods in transition are opportunities to foster the implementation of sustainability objectives within European metropolitan areas. This chapter explore this subject by deepening the sustainability issues at the neighbourhood scale. To provide the basis for discussion, we first attempt to frame the urban sustainability concept and to explain how the neighbourhood scale is a means of action for cities. Then, we analyse the different sustainability issues according to a wide variety of parameters that must especially be taken into account during sustainable neighbourhood projects, and more precisely urban brownfield regeneration projects. These parameters cover the four pillars of sustainability—the environment, society, economy, and governance—and the polycentric reorganization of European metropolitan areas.