Traditionally, industrial processes produce wastes that, even though often containing useful materials, are discarded, contributing to environmental pollution and depletion of natural resources. An example of such wastes are brines, flows of concentrated salts, produced in water treatment processes, which are now routinely discharged into receiving water bodies. Brines however can also be considered as flows of reusable materials which should be recovered, and the Zero Brine cooperation project aims to develop processes for that purpose. For a demineralized water production plant in the port of Rotterdam (the Netherlands), a closed water processing cycle was proposed to treat the large volume of spent Ion Exchange (IEX) regenerant brine which, apart from recovering demineralized water, is also intended to produce magnesium (Mg2+) and calcium (Ca2+) salts, with the highest purity possible, from the otherwise discharged brine. The process scheme includes nanofiltration (NF) for separating mono- and multivalent ions, followed by sequential chemical precipitation of Mg2+ and Ca2+ ions from the NF concentrate, and production of demineralized water by evaporation of the NF permeate. The concentrate of monovalent ions produced in the evaporator, essentially a concentrated sodium chloride solution, in its turn might be reused for IEX regeneration. Part of the supernatant of the sequential precipitation may be fed to the evaporator as well, but bleeding the other part of this supernatant is essential in order to maintain process stability, avoid accumulation of minor pollutants, and reduce scaling. In this study, various scenarios to operate the process were modeled, using PHREEQC and Excel. According to the simulation results, recovery of ≈97% of Mg2+ and Ca2+ is possible, the latter with a higher purity than the former. The main factors affecting the results are the concentration of carbonate present in the spent IEX regenerant, as well as characteristics of the NF membrane and the dosing of sodium hydroxide in the sequential precipitation steps. The results of the simulations were used for the design and operation of a pilot plant, comprising all mentioned process steps.