Pharmaceuticals and personal care products (PPCPs) are universally detected in natural waters, posing potential risks to drinking water safety. Nanofiltration (NF) is an advanced technology for water purification; however, its removals of PPCPs are unsatisfying, especially for hydrophobic species. In this study, the 3D architecture of nanomaterials were used to manipulate the performance the polyamide (PA) thin-film nanocomposite (TFN) membrane. In-situ addition of polyethyleneimine (PEI) successfully induced the assembly of ZIF-8 nanocrystals into star-shaped clusters (ZIF-8-PEI) due to the coordination between PEI and Zn2+. Together with the improved hydrophilicity, these ZIF-8-PEI clusters became excellent scaffolds for water drop retention after discretely loading onto the porous substrate. The conical protrusions of the ZIF-8-PEI clusters supported the defect-free PA film produced by the interfacial polymerization (IP), leaving big interfacial cavities underneath. These cavities worked as gutters for water transport, and the water permeance of the optimal TFN was 79% higher than that of the pristine thin-film composite (TFC) membrane. Moreover, the water impregnated cavities markedly alleviated the hydrophobic interaction between the PA film and hydrophobic PPCPs, impeding the transport of PPCPs across the membrane. Our results demonstrated the importance of the 3D architecture of nanofillers for the improving membrane performance.