An exergo-economic model is used to simulate four different feed configurations of multi-effect desalination with thermal vapor compressor (MED-TVC) system. The feed configurations considered are backward feed (BF), forward feed (FF), parallel feed (PF) and parallel cross feed (PCF). The model results indicate that the PCF configuration has better performance characteristics than the other feed configurations regarding gain output ratio (GOR) and specific heat consumption (SHC), but it has the highest specific cooling seawater flow rate (sM(cw)). On the other hand, the BF configuration has the lowest sM(cw). The highest exergy destruction (58%) occurs within the TVC unit and this can be reduced by lowering the supplied motive steam pressure. The exergy destructions in the condenser and pumps account for 4 to 6.7% of the total exergy destruction for all feed configurations. The MED-TVC under consideration has a second law efficiency between 3.9 and 4.6%. Lowering the motive steam pressure for the PCF from 2300 to 300 kPa results in a 7.5% reduction in GOR and a 25.4% increase in the second law efficiency. Reducing the exergy destruction in the TVC unit is cost-effective for the entire system even with the increase in capital investment costs. The specific exergy cost flow method is used to estimate the total water price for BF, FF, PF and PCF as 2.12, 2.30, 2.16 and 2.09 $/m(3), respectively.