Historically, the main actors in long-lived ports and cities have engaged with major transformations in interconnected ways creating buildings and urban spaces based on shared values. Over time they have established industrial areas, building, legal structures and business practices which are the result of purposeful collaboration and collective responses to opportunities and challenges. Over the last hundred years, with the separation of port and city, the economic dimension of the port has come to the fore, and spatial, cultural and economic links between port and city have weakened in many places. As each actor in the port-city-region space appropriately pursues their own goals—focusing on themes such as the optimization of logistics, innovative transportation, engineering of the port, or the balancing of societal questions such as economic development, infrastructural services, work conditions, health, education, or environmental issues—their spatial impact intersects with that of others. We propose that there is a need to work towards a sustainable coexistence at the port-city-region interface, that we need to understand common values, and that spatial concepts need to be developed that can facilitate contemporary relationships between the port and its environment and turn tensions into creative opportunities rather than conflicts.