Solving the low mineral/organic matter selectivity of nanofiltration (NF) membranes and realizing high permeability are effective strategies to satisfy the energy-saving production of high-quality drinking water. Controlling the interfacial polymerization (IP) reaction rate at the molecular level is a feasible approach to customize the functionality of NF membranes and simultaneously modulate multiple membrane properties. Here, we selected 1.4-piperazinediethanesulfonic acid (PIPES) as an aqueous-phase additive, and by taking advantage of the hydrogen-bonding, long-range electrostatic, and steric hindrance effects between PIPES and piperazine (PIP)monomers, as well as the reduction of solution pH, we achieved precise molecular-level regulation of the IP reaction rate. This strategy simultaneously enables the integrated tailoring of various membrane properties such as high hydrophilicity, high surface charge density, uniform pore size distribution and roughness reduction. Molecular dynamics (MD) and computational fluid dynamics (CFD) simulations were used to explore the effects of structural and morphological changes of the polyamide layer on the permeation performance, and the microscopic adsorption mechanism of foulants on the membrane was analyzed by a Quartz Crystal Microbalance (QCM). For pacificating natural surface water, the PIPES-0.75 NF membrane exhibited high permeation performance (23.7 LMH/bar), high mineral/organic selectivity (KCa2+/DOM = 16.5), excellent anti-fouling and anti-scaling properties, and reduced CO2 emissions per ton of water produced up to 90 %. In addition, an attempt was made to correlate the physicochemical properties of the membranes with the permselectivity and membrane fouling, and the economic availability of PIPES-conditioned NF membranes was examined, which provides a novel option for achieving NF in drinking water systems from the perspective of cost reduction and efficiency.