Studies on membrane fouling during treatment of oil refinery wastewater (ORW) via membrane bioreactor (MBR) are currently lacking, and associated fouling challenges are largely undocumented. Using advanced chemical and Illumina sequencing approach, we investigated the complex bio-physiochemical interactions responsible for foulant-membrane interactions during treatment of ORW. After nearly 2 months of the MBR operation, COD removal reached maximal of 97.15 ± 1.85%, while oil and grease removal was maintained at 96.6 ± 2.6%, during the treatment duration. Most of the less or non-biodegradable oil moieties (>0.5 μm) progressively accumulated on the membrane as the influent oil concentration increased. Presence of relatively higher unsaturated extracellular polymers (100.6 mg/g VSS) like fulvic acid and aromatic-like compounds at high volumetric loading (~18.7 kg COD/m3/d), enhanced the adsorption of chemical elements (Fe=88.9, Al=63.4, and Ce=0.56 mg/g dry-sludge, respectively). Moreover, shift in microbial community structure to hydrocarbon-utilizing and metals-tolerating genera, as Comamonas and Rhodanobacter, respectively, uncovers major membrane colonizers in ORW treatment via MBR.