Environmental health issues are multidimensional and multifactorial phenomena inherent with complex socio-spatial characteristics. Conventional GIS-based tools and analytical methods offer useful support for understanding the spatial characteristics of such issues but fall short when these are considered to be ‘wicked’ in nature and require the integration of various types of knowledge from a number of actors, for example both academics and practitioners. The knowledge, interests and values of various stakeholders that need to be integrated constructively may be confronted. This chapter describes two approaches developed for engaging stakeholders in the process of knowledge co-production and social learning on environmental health issues. The approaches, called the Interactive Spatial Support System (ISUSS) and Interactive Cumulative Burden Assessment (Interactive-CuBA), have been tested in two German case studies that were set up to support a stakeholder dialogue during the problem-understanding phase and while conducting cumulative burden assessment in the planning process, respectively. Building upon these two approaches, we present a conceptual framework to support knowledge co-production and social learning by an interactive GIS-based approach.