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The spatial structure of cities and regions is becoming more complex, and the socio-spatial interactions that occur in networks of cities seem to play an important role, influencing the economic potential of municipalities. This paper aims to present a methodology that allows analyzing the role of the regional spatial network configuration on the economic performance of the municipalities. The investigation is linked to urban morphology studies, using a systemic and quantitative approach from configurational studies. The network of cities in Rio Grande do Sul is taken as the empirical study. The spatial network model (graph) consists of municipalities (nodes) and highways (connections), allowing the calculation of accessibility and centrality measures. The results of these measures are then related to the economic attributes of the municipalities (GDP and GVA) through a statistical analysis of clusters. The empirical study revealed evidence that a good performance of the municipalities in the configurational network is associated with specific economic indicators: higher GDP, higher values of GVA for industry and services and lower values of agricultural GVA. The conclusions seek to discuss the potential and limitations of the proposed methodology to understand the regional spatial structure. [ABSTRACT FROM AUTHOR]