With the advancement in nanotechnology, we are experiencing transformation in world order with deep insemination of nanoproducts from basic necessities to advanced electronics, health care products and medicines. Therefore, nanoproducts, however, can have negative side effects and must be strictly monitored to avoid negative outcomes. Future toxicity and safety challenges regarding nanomaterial incorporation into consumer products, including rapid addition of nanomaterials with diverse functionalities and attributes, highlight the limitations of traditional safety evaluation tools. Currently, artificial intelligence and machine learning algorithms are envisioned for enhancing and improving the nano-bio-interaction simulation and modeling, and they extend to the post-marketing surveillance of nanomaterials in the real world. Thus, hyphenation of machine learning with biology and nanomaterials could provide exclusive insights into the perturbations of delicate biological functions after integration with nanomaterials. In this review, we discuss the potential of combining integrative omics with machine learning in profiling nanomaterial safety and risk assessment and provide guidance for regulatory authorities as well.