Managing energy, water, and environmental priorities and constraints within a cascade hydropower system is a challenging multi-objective optimization effort that requires advanced modeling and forecasting tools. Within the mid-Columbia River system, there is currently a lack of specific solutions for predicting how coordinated operational decisions can mitigate the impacts of total dissolved gas (TDG) supersaturation while satisfying multiple additional policy and hydropower generation objectives. In this work, a reduced order TDG uptake equation is developed that predicts tailrace TDG at seven hydropower facilities on the mid-Columbia River. The equation is incorporated into RiverWare, a general multi-objective river, reservoir, and hydropower optimization tool, as a prioritized operating goal within a broader set of system level objectives and constraints. A test case is presented to assess the response of TDG and hydropower generation when TDG supersaturation is optimized to remain under state water quality standards. Satisfaction of TDG as an operating goal is highly dependent on whether constraints that limit TDG uptake are implemented at a higher priority than generation requests. According to the model, an opportunity exists to reduce gas supersaturation and meet hydropower generation requirements by shifting spillway flows to different time periods. A coordinated effort between all project owners is required to implement system-wide optimized solutions that satisfy the operating policies of all stakeholders.