AbstractModeling the urban system for urban health and well-being with the aim of finding ways to optimize the well-being of urban dwellers is a complex task. Different modeling approaches that consider specific parts of the urban system, e.g., environmental stressors, urban society, and urban morphology, need to be integrated. The conceptual model of health-related urban well-being (UrbWellth) has been constructed to provide a structure for an integrated modeling framework. However, interfaces between the different modeling approaches were not sufficiently identified until now. The challenge to specify and operationalize these interfaces is met by using the Design Structure Matrix (DSM) concept, which is widely used in design engineering. It is used here to identify necessary interfaces within the urban system by determining the relevant interface variables and processes. The conceptual model for UrbWellth is used to construct a DSM. The results of a clustering of this UrbWellth-based DSM reveal that the structure of the conceptual model is indeed suitable to serve as a basis for an integrated model. Further, a Multi-Domain DSM (MDDSM), which is an extension of the DSM based on expert knowledge from individual modelers, identified the interface variables for the integrated model components as well as the processes for which different modeling approaches need to be coordinated. Moreover, the approach based on MDDSM identified processes that are not yet covered by the available modeling approaches.