Reverse osmosis (RO) membranes have been widely used in seawater desalination and drinking water preparation due to their outstanding ability to retain low valence salt ions and large organic molecules. Small neutral molecules (SNMs) are widely present in water, typically represented by boric acid in seawater and urea in wastewater. Reducing SNMs to meet drinking water standards is a new challenge for RO membranes. In this study, we developed a thin-film composite RO membrane tailored for seawater desalination, demonstrating exceptional selectivity against SNMs and heightened permeability. Specifically, a nonionic surfactant, flexible polyisobutylene succinimide (PIBSI), was added into the organic phase to react with trimesoyl chloride (TMC). The results showed that the new product, PIBSI–TMC, effectively exhibited the dual function of surfactant and co-monomer changed the physicochemical structure of PA formation during the interfacial polymerization process based on the detailed characterization. PIBSI integrated into the PA matrix significantly enhanced the hydrophobicity of the membrane surface and increased the specific surface area. Simultaneously, the pore size within the layer was reduced, and defects on the RO membrane surface were filled. The objectives were achieved by enhancing the size exclusion mechanisms effect, reducing SNMs diffusion rate, and ultimately improving selectivity. Experimental results demonstrated that the novel membrane achieved excellent desalination performance and a maximum boron removal efficiency of up to 90.40% in simulated seawater (32000 ppm NaCl, 5 ppm boron) compared to virgin membrane. The produced freshwater meets drinking water standards in various regions. Additionally, it exhibited higher flux (48.0 L m−2 h−1, 55.0 bar, approximately 26.4% permeate flux decline) compared to similar membranes. In addition, the rejection of SNMs in wastewater represented by urea was also effective. Therefore, it is favorable for application in resource recovery and pollutant removal. In conclusion, this novel RO membrane holds broad prospects for applications in seawater desalination and potable water production.