<p>Reverse osmosis (RO) membrane separation is vital for the advanced removal of contaminants, playing a key role in safe water supply. However, existing RO membranes fall remarkably short in adequate removal of small neutral organic contaminants (SNOCs ≤150 Da), due to the structural heterogeneity and nanosized defects of polyamide (PA) rejection layers. To address these challenges, we propose creating a continuous solid-phase interface using amphiphilic Cd^II/L-cysteine nanowires that spontaneously self-assemble at the water/n-hexane interface, thereby enabling precise control of the PA structure and suppressed formation of nanosized defects. The self-assembled Cd^II/L-cysteine interface facilitates the shuttling of m-phenylenediamine (MPD) monomers, achieving MPD pre-enrichment in the organic phase and leading to the formation of an ultraselective PA layer for the RO membrane, with an outstanding SNOC removal rate of up to 97.9%. Furthermore, the gutter effect and enhanced surface area ratio of the PA layer, induced by the Cd^II/L-cysteine interface, contribute to a remarkable increase in water permeance—upgraded by a factor of 4.5, reaching 3.6 ± 0.1 L m⁻² h⁻¹ bar⁻¹. This effectively breaks the trade-off between SNOC removal and water permeance. This work opens an appealing avenue for developing highly permeable and selective RO membranes for efficient water reuse.</p>