This work reports on the fundamental factors influencing inter-foulant and foulant-membrane interactions during simulated dissolved organic matter removal using ceramic nanofiltration. Fouling tests were performed using sodium alginate (SAL), humic acid (HA) and bovine serum albumin (BSA) as model foulants. Fouling potentials of each foulant and their mixtures were investigated using feed solutions containing fixed concentrations of K+, Na+, Mg2+ and Ca2+ with a total ionic strength of 10 mM. The impact of modification by atomic layer deposition on fouling mitigation was also assessed. The flux decline in the first 100 min for single foulants was 4.16 × 10−2, 2.69 × 10−2 and 1.60 × 10−2 Lm−2 for SAL, HA and BSA, respectively. These results demonstrated that for the single foulants, deposition on the membrane surface in the early stages of filtration was primarily governed by membrane-foulant interactions. Interestingly, cake filtration was the least fouling mechanism in feed solutions composed of BSA and SAL (R2 = 0.519, 0.374 for BSA + SAL and BSA + SAL + HA, respectively) and the most favorable fouling mechanism of feed solution which included HA and SAL (R2 = 0.972). The water contact angle dropped from 58o to 35° after coating, thus improving its anti-fouling properties.