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This work proposes an innovative approach of watershed level mercury trading for sustainable management of mercury pollution. An optimization based decision-making framework has been developed to optimize the selection of mercury treatment technologies by industries in a watershed in the presence of nonlinearity and uncertainty in technology cost models. The impact of the regulation on technology selection by industries, often ignored in existing trading literature, has been quantified. A particularly novel contribution of this framework is the consideration of health care cost as an objective. The application of the framework to the Savannah River watershed case study in US emphasizes the importance of health care cost while evaluating the benefits of trading. Nonlinearity and uncertainty in the cost models is shown to significantly affect technology selection. The ecological perspective of innovation comes from the proposal of using water body liming to mitigate mercury bioaccumulation and concerns of mercury hotspots.