Throughout Europe, cities and region are facing shrinkage. Shrinkage is usually indicated by population decline but is connected to many more issues. It is a complex process that can have negative consequences for both the social cohesion as well as the economic viability of a region. Shrinkage can also tear into the physical structure of our environment, creating neighbourhoods with excessive vacancy, industrial areas with brownfields and sparsely populated mountainous regions. Given that growth is no longer an option for many European cities and regions, we must adapt to this reality. The process of shrinkage will have a strong spatial impact on our cities and regions, and poses a challenge for spatial planners to keep cities and regions functional and liveable. However, planning and designing for shrinkage is a relatively new challenge, one for which we are still missing much expertise. As several academics have noted, shrinkage is not only a challenge, it is also an opportunity for cities and regions to reinvent themselves as more sustainable and ecologically sound places (Ferber & Schlappa, 2016; Haase, Haase, & Rink, 2014; Hollander, Pallagst, Schwarz, & Popper, 2009). The abundance of vacant land and buildings offer opportunities for less traditional land-uses, such as renewable energy, ecology, and agriculture (Hollander et al., 2009).What is currently lacking is a comprehensive approach that can capitalize upon these opportunities and scale them up to their full potential. That means finding the link between what could be done on a local scale, say on the scale of a vacant plot, and its implications for regional networks and structures. The discipline that is concerned with this activity is regional design (Neuman, 2000). The structure of this thesis is embedded in this discipline.The aim of this thesis is to generate a strategic regional design proposal that offers comprehensive steps for a sustainable regional transformation, responding to both the physical structure of the region as well as to the governance and planning frameworks. The design will identify the key potentials in the case-region and show how to best exploit them, with an emphasis on finding a synergy between the problems caused by shrinkage and opportunities for new forms of land use. The aim is to uncover new principles and strategies for spatial planning that can be transferred to other shrinking regions. Additional to the design will be an implementation strategy that considers the regional dynamic with regards to local planning systems and prominent stakeholders.