The quantitative structure–activity/property relationships (QSAR/QSPR) models are one of the efficient methods supporting the experimental investigations of chemicals, including nanomaterials and their risk assessment, as well as their application potential. This chapter focuses on the computational aspects of characterization of nanostructures in nano-QSAR/QSPR modeling and discusses various applied nanodescriptors. Nano-QSAR modeling was initiated as a result of research on the role of chemical composition in the final nanomaterial features. Independently to the first nano-QSAR models/recalculations, new types of nanodescriptors were developed for a variety physicochemical and biological endpoint. Designing new materials, including nanomaterials, requires knowledge about the physicochemical parameters responsible for the expected properties. Parameters of toxicity—genotoxicity, cytotoxicity, and ecotoxicity—are investigated using organisms at different trophic levels, that is, bacteria, algae, rodents, and mammals. In the context of toxicity modeling for nanomaterials, the first models were proposed by S. Kar et al. as interspecies nano-quantitative toxicity-toxicity relationship models.