With the rapid development of engineered nanomaterials (ENMs) in biomedical applications, their biocompatibility and cytotoxicity need to be evaluated properly. Recently, it has been demonstrated that inflammasome activation may be a vital contributing factor for the development of biological responses induced by ENMs. Among the inflammasome family, NLRP3 inflammasome has received the most attention because it directly interacts with ENMs to cause the inflammatory effects. However, the pathways that link ENMs to NLRP3 inflammasome have not been thoroughly summarized. Thus, we reviewed recent findings on the role of major ENMs properties in modulating NLRP3 inflammasome activation, both in vitro and in vivo, to provide a better understanding of the underlying mechanisms. In addition, the interactions between ENMs and NLRP3 inflammasome activation are summarized, which may advance our understanding of safer designs of nanomaterials and ENM-induced adverse health effects.