This work was aimed at conducting a multi-objective exergoeconomic and exergoenvironmental optimization of continuous synthesis of solketal through glycerol ketalization with acetone in the presence of ethanol as co-solvent and Purolite PD206 as catalyst. Exergoeconomic and exergoenvironmental performance parameters of the reactor were computed and discussed comprehensively after writing and solving their balance equations based on the experimental data. The effects of process parameters viz. ketalization temperature (T), acetone/glycerol molar ratio (X), feed flow rate (F), reaction pressure (P), and catalyst quantity (C) on the exergy-based variables were investigated in detail. The optimization process was performed based on minimizing two more important exergetic parameters, i.e., cost and environmental per unit of exergy for the product. To this end, an elaborated coupled version of adaptive neuro-fuzzy inference system (ANFIS) and non-dominated sorting genetic algorithm-II (NSGA-II) was employed. The ANFIS approach was used for modeling the process, while the NSGA-II was applied for finding the optimum operating conditions of the reactor. According to the results obtained, the ANFIS approach successfully predicted both objective parameters with an R-2 higher than 0.99. The optimum ketalization conditions for solketal synthesis in the developed reactor corresponded to T = 35.1 degrees C, X = 4.5, F = 0.4 mL/min, P = 26.7 bar, and C = 2.2 g, leading to the cost and environmental impact per unit of exergy for the product of 5032.9 USD/GJ and 143.9 mPts/GJ, respectively. (C) 2018 Elsevier Ltd. All rights reserved.