This paper presents a new systematic procedure to help process designers synthesizing a separation process that is economically efficient and environmentally sustainable. The proposed methodology is a hybrid method consisting of algorithmic and heuristic processing of symbolic and numeric data. The heuristic approach, applying experience-based rules and thermodynamic insights for selection of separation operations, is used to reduce the complexity and size of synthesis search space. The algorithmic approach using mathematical modeling is then used to formulate and solve the remaining problem. All environmental impacts are evaluated through all input and output of process and product life cycles. All criteria are simultaneously considered, and the multi-criteria optimization problem, which is formulated using existing computer-aided molecular design and selection tools, and computer-aided process design and analysis techniques, is solved to construct a trade-off set. The constructed trade-off set is then further analyzed to select a promising solution. The proposed methodology is implemented using available software tools. Application of developed methodology is illustrated in a case study. We investigate process for phenol recovery from wastewater. This process is used in phenolic-resin manufacturing. The developed methodology can select solutions that are minimal environmental impacts at a desired economic performance.