The presence of an economically stronger neighbor can affect a region’s development path in a variety of ways, some positive and some negative. In this dissertation, I investigate how regional economic development actors attempt to leverage the potential advantages and mitigate the potential disadvantages of proximity to a stronger region. This research contributes actor-focused, planning-centered perspectives to an emerging literature that seeks to explain and predict interregional economic relationships. Understanding these relationships, and how actors attempt to shape them, is particularly important given widespread patterns of growing interregional economic divergence that threaten social and political stability. In the dissertation’s introduction, I place the research questions within the context of theoretical and empirical literature on interregional economic relationships, and identify key themes that inform the three chapters’ research questions and design. I discuss the dissertation’s contributions to the academic understanding of regional economic development paths and to the development of tools that can be used to bridge this research with policy and practice. All three chapters of the dissertation engage in mixed methods case study based in the Upper Rhine megaregion, which spans three countries and nine economically diverse subnational regions. The Upper Rhine provides the opportunity to study interactions between stronger and weaker neighboring regions, including separating out the effects of national and regional institutional contexts. The first chapter of the dissertation examines cross-border interregional integration, comparing spatial patterns of functional integration, in the form of commuter flows, with those of organizational integration, indicated by network ties among economic development organizations. I find that the presence of pronounced differentials in wages and cost of living shape both forms of integration, but in different ways. While functional flows are driven by the presence of differentials, organizational networks and network strategy reflects attempts by development actors to capture benefits of complementarity or similarity with their counterparts across international borders. These organizational networks also reflect a broad context of formal and informal institutional integration. In the second chapter, I compare how economic development actors in two regions attempt to spatially position their region versus a stronger neighbor, and relate their strategic choices to theoretical models of interregional economic relationships. I find that these actors simultaneously attempt to avoid or reduce threats posed by their strong neighbor, and attempt to capitalize on opportunities provided. Drawing from the findings, I also clarify a definition for “spatial positioning” and argue for its relevance as a planning concept. The third chapter examines how economic development practitioners engage with the concept of place competitiveness in the context of interregional disparities. Findings indicate that competitiveness is an incoherent concept; actors used a range of definitions and operationalizations, some of which were contradictory. While market-based logics dominated discussion of competitiveness, actual strategy and application indicated more diverse approaches to economic development, including significant emphasis on collaboration. I untangle two factors which determine whether development approaches are competitive or collaborative: the scale at which they occur and the scarcity of the resources involved. In each chapter, I connect theoretical literature and empirical research with potential policy application. I offer typologies or frameworks intended to draw out the underlying mechanisms shaping interregional relationships, and interrogate concepts that actors are expected to implement in economic development practice. To conclude, I suggest future directions for this line of inquiry, and situate the research within the context of current challenges in regional development.