Brine from desalination plants is an upcoming environmental threat to aquatic ecosystems. Multi-effect distillation with thermal vapor compression (MED-TVC) is proposed to treat desalination brine solutions of more than 70 000 mg/L of total dissolved solids (TDS). To achieve this, an integrated techno-economic model consisting of three submodels (scaling prediction, mathematical, and economic) is developed and a techno-economic assessment of a 10 m(3)/d MED-TVC system is presented under two different scenarios. In this respect, various sensitivity analyses were performed, revealing that the 4-effect MED-TVC system operating at 120 degrees C feed steam presents the lowest freshwater cost (US$3.00/m(3)) and the lowest payback period (3.04 years) under the first scenario, whereas the 2-effect MED-TVC system operating at 120 degrees C feed steam presents the lowest freshwater cost (US$1.69/m(3)) and the lowest payback period (1.71 years) under the second scenario of waste heat utilization. Exergy analysis for these optimal systems revealed that the exergy efficiency of the optimal system in the second scenario (4.36%) is higher than in the first scenario (4.21%). For both optimal systems, the exergy destruction in the TVC unit and in the effects accounts for more than 79% of the total exergy destruction. Moreover, it was found that thermal energy costs contribute significantly to the costs and affect the design procedure. Scaling up the optimal systems for freshwater production by more than 190 m(3)/d, freshwater cost becomes constant and can be reduced by up to 50% with waste heat integration. Considering the high quality of the freshwater produced, MED-TVC process can be profitable due to the revenue from the sale of the freshwater. Overall, the results suggest that the MED-TVC process for brine treatment is economically feasible.