A performance simulator of spiral wound membrane (SWM) modules used for desalination is a valuable tool for process design and optimization. The existing state-of-the-art mesoscale simulation tools account for the spatial non-uniformities created by the operation itself (flow, pressure, and concentration distributions) but they assume uniform membrane properties. However, experimental studies reveal that membrane properties are by no means uniform. Therefore, the need arises to account for this non-uniformity in simulation tools thus enabling a systematic assessment of its impact, among other benefits; a first step toward this goal is presented herein. In particular, the issue of an organic fouling layer growing on a membrane with non-uniform permeability is analyzed. Several mathematical treatments of the problem are discussed and indicative results are presented. The concept of fouling layer thickness probability density function is suggested as a means to introduce sub-grid level calculations in existing simulation tools. The analysis leads to the selection of an appropriate methodology to incorporate this effect in the dynamic simulation of fouling layer evolution at the membrane-sheet scale.