Organic fouling in the RO tertiary desalination process is of major concern in the decline in membrane performance. Mitigation of such fouling scenarios were shown in lab scale by biofiltration and UF pretreatments and compared to the associated EfOM composition as analyzed and quantitatively fractionated in LC-OCD-OND chromatography. While assuming that changes in the EfOM composition due to different pretreatment steps, will lead to differences in membrane fouling, we showed that size and charge are limited in their importance in organic fouling scenarios. Effects of UF pretreatment were observed reducing biopolymer quantity of the total EfOM and thus impacting its affinity to the membrane. Biofiltration pretreatment reduced the hydrophobic fraction of the EfOM. As a major observation it was shown, that the adhesion of different LC-OCD-OND fractions to polyamide was similar, regardless their origin. The highest adhesion was observed for the biopolymers, while the lowest one was observed for the lower molecular weight humics (hundreds of Da) and building blocks. The presence or absence of biopolymers, could possibly explain the differences in the observed membrane performance, as deduced from combination of LC-OCD-OND and QCM-D analyses. However, this study indicates, that other quantitative fractionation approaches, based on compounds hydrophobicity should be carried out. Combination of size, charge and hydrophobicity-based fractionation with adhesion analysis using QCM-D and AFM can provide a robust approach to gain deeper knowledge in EfOM fouling control strategies and optimization of the RO desalination pretreatment stage.