In this study, exergy analysis of four different feed configurations of a multi-effect desalination with mechanical vapor compressor (MED-MVC) system is initially studied to identify the area of exergy destruction within system components and followed by an exergo-economic study. The feed configurations considered are forward feed (FF), backward feed (BF), parallel feed (PF) and parallel/cross feed (PCF). From the 1st law energy analysis, the PCF and FF configurations require less work to achieve equal distillate production compared to other two configurations. For instance, the specific power consumption (SPC) values are 30.1, 13.7, 23 and 13.9 kWh/m(3) for the BF, FF, PF and PCF configurations, respectively. Changing the feed arrangement from BF to FF and PF to PCF at a constant compression ratio, the total fixed cost for the MED-MVC plant can be reduced by similar to 30% and 17%, respectively. Second law efficiency (eta(II)) calculations show that the PCF (2.9%) has the highest value followed by the FF (2.7%), while the BF (2.4%) exhibits the lowest value among all configurations. The highest exergy destruction (35-50%) occurs within the MVC unit. This can be reduced by limiting the design plant operation to a lower temperature range or increasing the number of effects. Increasing the number of effects for PCF from 1 to 6 results in a 39% reduction in the SPC and a 70% increase in the second law efficiency. Operating at lower steam temperature results in an increase in the eta(II), and a decrease in the SPC and total water price (TWP) of the MED-MVC system. Reducing the exergy destruction in the preheaters and the MVC unit is cost-effective for the entire system even with an increase in capital investment costs. Three different cost models are used to estimate the average TWPs for the BF, FF, PF and PCF configurations, and the TWPs are found to be 3.0, 1.7, 2.4 and 1.7 $/m(3), respectively. (C) 2018 Elsevier Ltd. All rights reserved.