<p>Synergistic-tuning the permselectivity and chemical stability of polymer membranes with a scalable method is an imminent demand for sustainable and energy-efficient organic solvent nanofiltration, but remains an intricate challenge. Here, we report a bifunctional molecular engineering strategy to fabricate sub-20 nm fluorinated polyamide nanofilms via scalable interfacial polymerization. Experiments and molecular simulations reveal that in situ incorporation of noncoplanar contorted segments with hydrophobic fluorine-rich pendants into a flexible hydrophilic polyamide backbone constructs a highly crosslinked 3D interconnected Janus microporous framework with rigid–flexible and hydrophilic–hydrophobic duality. This Janus structure instigates simultaneous control over the dissolution and migration of polar and nonpolar organic solvents. The resulting membranes exhibit enduring chemical stability, unprecedentedly high solvent permeance, and concomitantly low molecular weight cutoff, rivaling state-of-the-art membranes. This work provides a promising paradigm for the development of high-performance membranes to promote the sustainability of energy-intensive filtration of organic solvents over a wide range of solvent polarity.</p>