This paper describes the spatiotemporal epistematics knowledge synthesis and graphical user interface (SEKS–GUI) framework and its application in medical geography problems. Based on sound theoretical reasoning, the interactive software library of SEKS–GUI explores heterogeneous (spatially non-homogeneous and temporally non-stationary) health attribute distributions (disease incidence, mortality, human exposure, epidemic propagation etc.); expresses the health system’s dependence structure using (ordinary and generalized) spatiotemporal covariance models; synthesizes core knowledge bases, empirical evidence and multi-sourced system uncertainty; and generates a meaningful picture of the real-world system using space–time dependent probability functions and associated maps of health attributes. The implementation stages of the SEKS–GUI library are described in considerable detail using appropriate screens. The wide applicability of SEKS–GUI is demonstrated by reviewing a selection of real-world case studies.