This work presents a joint experimental and simulation campaign aimed at characterizing two nanofiltration membranes (TS80 and NF270) in the presence of a multi-ionic water solution simulating the spent regenerant of cationic ion exchange resins employed for water softening. We identified the membrane parameters, which allowed for predicting the performances through the Donnan Steric Pore Model with Dielectric Exclusion. A good agreement between model and experimental trends of rejection as a function of the applied pressure was observed (error < 15%). The analysis of trans-membrane fluxes and exclusion coefficients showed that dielectric exclusion was the crucial mechanism for the ionic partition. In fact, the lower pore dielectric constant found for TS80 justified the higher rejections to divalent cations with respect to NF270. Moreover, negative charge densities were found for both membranes, because of the high concentration of chloride ions in the feed, which likely adsorbed onto the membrane. However, it was observed that the experimental rejections did not change significantly with the feed pH. This result, in line with the minor role of the Donnan exclusion resulting from the model, suggested that the membrane performances were not much affected by the charge density at high feed ionic strengths (~1 M).