Thin-film composite (TFC) membranes featuring nanovoid-containing polyamide (PA) layers on supportive nanofiber substrates represent a significant advancement in desalination technology. However, the separation performance of TFC membranes hinges critically on the nanoscale thickness of the PA layers and their distinctive ridge-and-valley roughness. This complex morphology is a direct result of interfacial instability arising during the highly exothermic interfacial polymerization (IP), where heat generation drives non-uniform PA layer growth. To mitigate these instabilities that adversely affect the overall membrane performance, thermally conductive MXene (Ti3C2Tx) nanosheets are spray-coated onto the supportive polymeric substrates before initiating the IP process. The MXene-coated substrate significantly improves the surface morphology of the PA layer, reducing its thickness to 18 nm and minimizing nanovoid formation due to the effective lateral heat dissipation by the Ti3C2Tx MXene interlayer. These interlayers regulate monomer diffusion via hydrogen bonding and covalent interactions, ensuring uniform polymerization and defect-free PA layers. The optimized Ti3C2Tx MXene-interlayered TFC membrane exhibits a more than two-fold increase in the water flux, exceeding that of commercial membranes, while significantly improving ion rejection. This study highlights the significant impact of substrate thermal conductivity on desalination efficiency, enabling the development of smooth and efficient PA nanofilms for high-performance desalination through the tailored design of interlayered TFC membranes.