Contamination of water bodies by acid mine drainage (AMD) from mining industries is affecting global freshwater availability, especially in arid zones like northern Chile. A real AMD from a contaminated Chilean river was used in this study. This work aimed to evaluate an economic projection of a Forward Osmosis–Membrane Distillation (FO-MD) process versus a Forward Osmosis–Reverse Osmosis (FO-RO) for an AMD treatment. FO-MD continuous assays (12 h) were performed using AMD solution as feed and NaCl as draw solution, achieving an initial flux of 25 LMH with FO and a stable flux around 10 LMH for MD. Different FO-MD economic models were developed using steam and thermal-fluid as heat-source. The cost assessment showed that thermal-fluid FO-MD has a payback period of 1.8 years with a water cost of 3.36 $/m3 while FO-RO's investment return was one year with a water cost of 1.47 $/m3. A Monte Carlo modeling results identified the membrane cost and the thermal energy expense as the elements with the highest impact on the economic indicators. Nevertheless, the economic assessment revealed that if waste-heat is available, the FO-MD operation cost would be lower than FO-RO's (1.29 $/m3), even with today's high FO/MD membrane cost.