The issue of environmental sustainability has prompted the batch chemical industries to switch from end-of-pipe treatment to waste minimization as top priority in tackling the pollution problem. In this paper, we introduce a novel simulation-optimization framework that integrates different process systems engineering (PSE) methodologies – process graph (P-graph), hierarchical design strategy, WAR algorithm, source-sink allocation method, and multi-objective optimization as decision making tools for waste minimization analysis. The framework is applied to a well-known literature case study and yields convincing results.