On the opposite end of the spectrum, high-fidelity, commercial process simulators (e.g., GPS-X TM , 220 Aspen Plus ® , 221 SuperPro Designer, 222 AnyLogic 223 ) with rigorous design and process algorithms have been widely used for system design and simulation, especially for largescale, multi-unit process systems (e.g., wastewater treatment trains, 224,225 bio-or chemical refineries ). Supported by commercial companies, these simulators are well-tested and capable of solving complex algorithms, allowing deeper investigation into the dynamics among the QSD inputs, system inventory, and sustainability. However, because of their proprietary nature, these simulators are often less accessible and transparent. They may have also limited flexibility to evaluate early-stage technologies due to the lack of corresponding unit operations and associated design and process algorithms. Moreover, many of these simulators have no or limited capacity for advanced statistical analyses (e.g., global sensitivity analysis beyond correlation and regression methods). Thus, they often cannot independently fulfil the objectives of QSD studies.