Integrated exergetic, data envelopment analysis (DEA)-robust parameter design framework is proposed to optimize and select thermo-feasible multicomponent distillation system which is a herculean task through reported exergy analysis techniques. It attempts to reduce the thermodynamic computational search for optimal sequence and to handle the effects of variations. Conventional exergetic analysis obtained the thermo-responses, variations are smoothened by robust signal-to-noise ratio procedures, variable return to scale (VRS) partitioning is imposed prior to the efficiency determination by the facet VRS model and penalization coefficient model is employed to select the optimum. The numerical illustration reveals its specificity and provides vivid and panoramic insight into actual efficient systems and those that need improvement. This study shows that exergetic analysis when integrated with DEA and robust parameter procedures can interrelate adequately, efficiently and effectively to optimize multicomponent distillation process and can be applied for optimizing energy-intensive systems especially those with multi-response processes.