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Today, the location of a business is more important than ever, as it contributes to its consolidation in the market and, in parallel, to the economic development of a city. Over the years, the theories about the optimal location of a business have undergone various changes, both financial and spatial. On the other hand, economic geography, as a discipline that studies the distribution of economic activities as well as the interactions between them, is also an important tool for the analysis of urban/spatial and business processes. This paper finds the optimal locations of economic activities through the combination of theories of economic geography and spatial analysis, for the sake of reducing urban shrinkage and increasing the resilience of businesses and cities. The analysis of this paper proved that the areas that are most exposed to urban shrinkage are the least central areas. Urban shopping centers, despite the large percentage of closed stores, continue due to their centrality to attracting more new businesses. The calculation of the optimal location of the economic activity showed that the optimal location depends on the financial sector itself but also on the economic activities that open or close over time in this region. In this way, an answer is sought regarding the way in which each region and its economic identity can influence a city’s future development and resilience. Thus, through this analysis, cities are able to control and strengthen their economic landscapes, vulnerable as they are in difficult times, and to implement policies in specific urban units, with a view to the prosperity of their economic activities.