Flocculation is a mainstream technology for the provision of safe drinking water but is limited due to the ineffectiveness of conventional flocculants in removing trace low-molecular-weight emerging contaminants. We described a synthesis strategy for the development of high-performance nanoflocculants (hydrophobic-organic-chain-modified metal hydroxides [HOC-M]), imitating surfactant-assembling nano-micelles, by integration of long hydrophobic chains with traditional inorganic metal (Fe/Al/Ti)-based flocculants. The core-shell nanostructure was highly stable in acidic stock solution and transformed to meso-scale coagulation nuclei in real surface water. In both jar and continuous-flow tests, HOC-M was superior over conventional flocculants in removing many contaminants (turbidity, UV254, and DOC: >95%; TP and NO3-N: >90%; trace pharmaceuticals [initial concentration: 100 ng/L]: >80%), producing flocs with better structural and dewatering properties, and lowering the environmental risk of metal leaching. The rationally designed nanoflocculants have large application potential, as a solution to increasing public concern about micro-pollutants and increasing water quality requirements.