Radiolabeled metal-based nanoparticles (MNPs) have drawn considerable attention in the fields of nuclear medicine and molecular imaging, drug delivery, and radiation therapy, given the fact that they can be potentially used as diagnostic imaging and/or therapeutic agents, or even as theranostic combinations. Here, we present a systematic review on recent advances in the design and synthesis of MNPs with major focuses on their radiolabeling strategies and the determinants of their in vivo pharmacokinetics, and together how their intended applications would be impacted. For clarification, we categorize all reported radiolabeling strategies for MNPs into indirect and direct approaches. While indirect labeling simply refers to the use of bifunctional chelators or prosthetic groups conjugated to MNPs for post-synthesis labeling with radionuclides, we found that many practical direct labeling methodologies have been developed to incorporate radionuclides into the MNP core without using extra reagents, including chemisorption, radiochemical doping, hadronic bombardment, encapsulation, and isotope or cation exchange. From the perspective of practical use, a few relevant examples are presented and discussed in terms of their pros and cons. We further reviewed the determinants of in vivo pharmacokinetic parameters of MNPs, including factors influencing their in vivo absorption, distribution, metabolism, and elimination, and discussed the challenges and opportunities in the development of radiolabeled MNPs for in vivo biomedical applications. Taken together, we believe the cumulative advancement summarized in this review would provide a general guidance in the field for design and synthesis of radiolabeled MNPs towards practical realization of their much desired theranostic capabilities. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.