This review, published in the Chemical Reviews virtual special issue "Ionic Liquids for Diverse Applications," focuses on the role of process simulations in advancing the development of ionic liquid (IL)-based technologies. ILs are promising alternatives for solvents and catalysts due to their unique properties, such as tunability and high thermal stability. The review highlights the importance of integrated product and process designs to select optimal ILs for industrial applications, emphasizing the shift from experiment-oriented to hybrid experimental-computational approaches guided by process engineering. The review covers the application of robust simulation methodologies, primarily based on predictive COSMO-SAC/R5 and UNIFAC models in Aspen Plus software, to analyze key IL applications, including CO2 capture, gas separation, liquid-liquid extraction, extractive distillation, refrigeration cycles, and biorefinery. It discusses the contributions in IL selection criteria, operational unit design, equipment sizing, techno-economic and environmental analyses, and process optimization. The methodology for applying process simulations to ILs is detailed, including the definition of IL compounds, thermodynamic models, property models, operation unit models, process modeling, and optimization. The review also addresses the limitations and future challenges in process simulation, emphasizing the need for more comprehensive experimental data and advanced computational methods to enhance the reliability and applicability of IL-based technologies. Overall, the review underscores the significance of process simulations in advancing the technological development of IL-based applications, enabling the selection of optimal ILs, and guiding experimental research efforts to promote cost-effective and sustainable technologies.This review, published in the Chemical Reviews virtual special issue "Ionic Liquids for Diverse Applications," focuses on the role of process simulations in advancing the development of ionic liquid (IL)-based technologies. ILs are promising alternatives for solvents and catalysts due to their unique properties, such as tunability and high thermal stability. The review highlights the importance of integrated product and process designs to select optimal ILs for industrial applications, emphasizing the shift from experiment-oriented to hybrid experimental-computational approaches guided by process engineering. The review covers the application of robust simulation methodologies, primarily based on predictive COSMO-SAC/R5 and UNIFAC models in Aspen Plus software, to analyze key IL applications, including CO2 capture, gas separation, liquid-liquid extraction, extractive distillation, refrigeration cycles, and biorefinery. It discusses the contributions in IL selection criteria, operational unit design, equipment sizing, techno-economic and environmental analyses, and process optimization. The methodology for applying process simulations to ILs is detailed, including the definition of IL compounds, thermodynamic models, property models, operation unit models, process modeling, and optimization. The review also addresses the limitations and future challenges in process simulation, emphasizing the need for more comprehensive experimental data and advanced computational methods to enhance the reliability and applicability of IL-based technologies. Overall, the review underscores the significance of process simulations in advancing the technological development of IL-based applications, enabling the selection of optimal ILs, and guiding experimental research efforts to promote cost-effective and sustainable technologies.