Protection of the environment and people from the potential impacts of uranium mining and milling is a global issue as the world's demand for power generation derived from uranium increases. We present a framework for deriving multiple stressor-pathway causal models for an operational uranium mine that can be used to identify research and monitoring needs for environmental protection. Additionally the framework enabled us to categorise the importance of pathways in the system. An interdisciplinary approach to causal model development was undertaken in order to ensure the potential impacts of mining on the natural environment and human health were identified and assessed by researchers with the appropriate knowledge. An example of a causal model and supporting narrative is provided for the most important stressor pathway, transport of inorganic toxicants via the surface water to surface water pathway. This risk-based screening approach can be applied to mining operations where environmental protection (including human health) is underpinned by quantitative interdisciplinary research and monitoring.