To solve the scarcity of fresh water, reverse osmosis (RO) technology for seawater desalination and wastewater reuse has been developed rapidly. However, the performance of RO is limited by poor selectivity towards certain harmful small molecule constituents (e.g., boron in seawater and N-nitrosodimethylamine in wastewater) and the permeability-selectivity trade-off. Herein, a metal polyphenol network interlayer including both hydrophobic zone and monomer adsorption zone is proposed to optimize interfacial polymerization (IP) process for fabrication of RO membrane. This heterogeneous characteristic is endowed by well-chosen phenol (i.e. TTSBI) and metal (Ni). The physicochemical properties of the substrate are also optimized. An ultra-selective RO membrane with thinner separation layer, higher crosslinking degree and larger surface area is obtained. The RO membranes exhibit separation performance beyond the upper selectivity limit for NaCl and hazardous small molecules. The membrane water permeance is 3.50 L m−2h−1bar−1while the NaCl rejection is 99.5 %. Meanwhile, the mechanism of the interlayer influencing IP process is investigated by combining molecular simulation and experimental methods. Our work provides a novel design direction of substrate used for fabricating RO membrane with outstanding performance.