Understanding the dynamics of water-energy-food (WEF) nexus interactions with climate change and human intervention helps inform policymaking. This study demonstrates the WEF nexus behavior under ensembles of climate change, transboundary inflows, and policy options, and evaluates the overall nexus performance using a previously developed system dynamics-based WEF nexus model—WEF-Sask. The climate scenarios include a baseline (1986-2014) and near-future climate projections (2021-2050). The approach is demonstrated through the case study of Saskatchewan, Canada. Results show that rising temperature with increased rainfall likely maintains reliable food and feed production. The climate scenarios characterized by a combination of moderate temperature increase and slightly less rainfall or higher temperature increase with slightly higher rainfall are easier to adapt to by irrigation expansion. However, such expansion uses a large amount of water resulting in reduced hydropower production. In contrast, higher temperature, combined with less rainfall, such as SSP370 (2.4 ℃, -6 mm), is difficult to adapt to by irrigation expansion. Renewable energy expansion, the most effective climate change mitigation option in Saskatchewan, leads to the best nexus performance during 2021-2050, reducing total water demand, groundwater demand, greenhouse gas (GHG) emissions, and potentially increasing water available for food production. In this study, we recommend and use food and power production targets and provide an approach to assessing the impacts of hydroclimate and policy options on the WEF nexus, along with suggestions for adapting the agriculture and energy sectors to climate change.