Updated project metadata. Current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we pioneered a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows visualizing the contributions of 7 basic properties of Fe2O3 to its diverse bio-effects. For instance, while surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs were examined in THP-1 cells and animal lungs, which allowed us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1 dependent signaling. This study provides new insights for nano-SARs, which may facilitate the tailored design of ENMs to endow them with desired bio-effects.