The widespread commercial use of TiO2-NPs, such as in medical stents, has led to extensive investigations on their toxicity and biological impact but lacks a detailed study on their effects. Proteomics and transcriptomics are key methodologies to unravel cellular dynamics, macromolecular interactions and biological response to NP exposure through the protein or gene identification and quantification. We focus on integration of several Omics strategies that could offer a more complex understanding of the impact. In this study, our goal was to gain insight into the cellular response after the exposure to sublethal concentration of TiO2-ultra small nanoparticles (USNPs) and NPs by analyzing the modification on the genomic and proteomic expression in human microdermal endothelial cells (HMEC-1). We investigated the correlation between the NP size and the cellular response to the exposure. We evaluated if multiOmics approaches could thus reveal more extensive information on the potential cellular responses to NPs exposure.