Updated project metadata. Here, we investigated a panel of 31 engineered nanomaterials (ENMs) with different core chemistries and surface modifications using conventional cytotoxicity assays coupled with omics-based approaches. Proteomics analysis were conducted in order to monitor changes in cells proteome exposed to ENMs. In this standard approach, cells are exposed to various types and amounts of ENMs and proteins are extracted after a given exposure period. For controls, no ENM are applied but the incubation and extraction of proteins is done the same way. Proteome changes are monitored using high-resolution Fourier transform mass spectrometry (Orbitraps) as well as in-house developed label-free software. Similar approaches have been used for quantitative analysis of posttranslational modifications. Proteomics analyses following low-dose exposure of THP-1 cells suggested a non-specific stress response to ENMs while microarray-based profiling revealed significant changes in gene expression as a function of both surface functionalization and core chemistry of the ENMs. Pathway analysis revealed that the most biologically active ENMs displaying cationic surfaces downregulated DNA replication/cell cycle responses and upregulated inflammatory responses. This study shows that surface chemistry is a key determinant of nanomaterial effects on immune cells.