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The objective of this study is to develop a framework for re-examining and re-defining the classical concepts of spatial inter-action and reorganization in the urban system. We introduce a modified radiation model for spatial interactions, coupled with migration big data, transport accessibility algorithm, and city competitiveness assessment for efficient distribution of the inter-city flow through the network. The Yangtze River Middle Reaches (YRMR) urban agglomeration (UA) is chosen as the case study region to systemati-cally identify and measure its spatial configuration and to gain insights for other UAs' sustainable development in China. The results are also compared with those computed by the classical gravity model to systematically discuss the applicability of spatial interaction laws and models, and related practical policies for regional sustainable development are discussed based on the findings as well. The conclu-sions are highlighted below: 1) Combining with the 'city network paradigm' and 'central place theory' can better express the spatial configurations of city systems in the context of 'space of flows'; 2) The results validate the potentialities of a multi-analysis framework to assess the spatial configurations of city network based on the improved radiation model and network analysis tools; 3) The applica-tions of spatial interaction models should be considered according to the specific geographical entity and its spatial scale.