In past decades, many cities and regions have underwent structural transformations—e.g., in old industrialized “rust belts” or in peripheral rural areas. Many of these shrinking cities have to face the challenges of long-term demographic and economic changes. While shrinkage is often related to post-industrial transformations in the USA, in other countries, such as Germany, for example, the causes are related to changing demographics with declining birth rates and the effects of the German reunification. Many cities have tried to combat shrinkage and have thus developed a variety of policies and strategies such as the establishing of substitute industries. To assess the sustainability of this approach, this paper investigates the cities of Cleveland, USA and Bochum, Germany in a comparative analysis following the most similar/most different research design. The paper shows that substitute industries might lead to new development paths for shrinking cities; however, whether these paths stimulate sustainable development is dependent on those who are benefiting from these developments and to what extent.