Potential human health risk from waterborne diseases arising from unsatisfactory performance of on-site wastewater treatment systems is driven by landscape factors such as topography, soil characteristics, depth to water table, drainage characteristics and the presence of surface water bodies. These factors are present as random variables which are spatially distributed across a region. A methodological framework is presented that can be applied to model and evaluate the influence of various factors on waterborne disease potential. This framework is informed by spatial data and expert knowledge. For prediction at unsampled sites, interpolation methods were used to derive a spatially smoothed surface of disease potential which takes into account the uncertainty due to spatial variation at any pre-determined level of significance. This surface was constructed by accounting for the influence of multiple variables which appear to contribute to disease potential. The framework developed in this work strengthens the understanding of the characteristics of disease potential and provides predictions of this potential across a region. The study outcomes presented constitutes an innovative approach to environmental monitoring and management in the face of data paucity. (C) 2016 Elsevier B.V. All rights reserved.