The rapidly growing applicability of metal-containing engineered nano particles (MENPs) has made their environmental fate, biouptake, and transformation important research topics. However, considering the relatively low concentration of MENPs and the high concentration of background metals in the environment and in organisms, tracking the fate of MENPs in environment-related scenarios remains a challenge. Intrinsic labeling of MENPs with radioactive or stable isotopes is a useful tool for the highly sensitive and selective detection of MENPs in the environment and organisms, thus enabling tracing of their transformation, uptake, distribution, and clearance. In this review, we focus on radioactive/stable isotope labeling of MENPs for their environmental and biological tracing. We summarize the advantages of intrinsic radioactive/stable isotopes for MENP labeling and discuss the considerations in labeling isotope selection and preparation of labeled MENPs, as well as exposure routes and detection of labeled MENPs. In addition, current practice in the use of radioactive/stable isotope labeling of MENPs to study their environmental fate and bioaccumulation is reviewed. Future perspectives and potential applications are also discussed, including imaging techniques for radioactive- and stable-isotope-labeled MENPs, hyphenated multistable isotope tracers with speciation analysis, and isotope fractionation as a MENP tracer. It is expected that this critical review could provide the necessary background information to further advance the applications of isotope tracers to study the environmental fate and bioaccumulation of MENPs.