This chapter summarizes the knowledge on nano-quantitative structure–activity relationship (QSAR) for metal-based engineered nanomaterials (ENMs) with regard to sources of data, existing nano-QSARs, mechanistic interpretation, and an outlook on the opportunity for further development of this frontier. It aims to present key advances in relevant nanomodeling studies and to stimulate future research efforts in the quickly developing field of computational hazard assessment of ENMs. The rapid development of nanotechnology and extensive use of ENMs for industrial and commercial applications have caused safety concerns. The uptake of nanomaterials may lead to adverse effects, and there is consensus across a variety of studies regarding the occurrence of damage triggered by ENMs at the cellular level. The limited data availability on ENM hazards necessitates the need of extending conventional QSAR approaches to nanotoxicology, that is, nano-QSARs. Facing the strong need for extending the conventional QSAR approach to nanotoxicology, some attempts have been made to link ENMs’ biological effects with the characteristics of ENMs.