The fouling layers on heat exchanger surfaces exhibit complicated structures, which essentially affect flow hydrodynamics, fouling kinetics, and hence the heat transfer performance. Numerical models developed so far for the fouling process, however, are based exclusively on the assumption of an impermeable fouling layer with a uniform porous structure. In order to quantitatively evaluate the effect of fouling layer structure on fouling dynamics, this work systematically investigated four representative schemes for fouling layer characterization: a homogeneous porous medium that is impermeable to water (HoIm), a heterogeneous porous medium that is impermeable to water (HeIm), a homogeneous porous medium that is permeable to water (HoPe), and a heterogeneous porous medium that is permeable to water (HePe). Under the same operational conditions, four models offer significantly different prediction results on the fluid velocity, temperature distribution, and fouling resistance. It is concluded that numerical model development should take the fouling layer structure into account, and the scheme of HePe that best resembles a real fouling layer structure should be a promising option.