Spectral CT imaging (multi-energy detection) is a promising imaging technique that can benefit from the use of high atomic number (high-Z) based nanoparticles (NPs) as contrast agents. These NPs can improve image contrast and enable quantitative material reconstruction, potentially leading to more accurate diagnoses and better treatment planning. This article provides an overview of current research on the use of high-Z NPs for spectral CT imaging. This briefly covers the physicochemical properties and biocompatibility of eight high-Z elements: gadolinium, ytterbium, hafnium, tantalum, tungsten, rhenium, gold, and bismuth. This article also focuses on various in vitro, in vivo, and simulation studies that have investigated the potential advantages and limitations of using high-Z NPs as contrast agents for spectral CT imaging. In addition, the review also highlights the potential preclinical and clinical applications of high-Z NPs in cancer diagnosis, therapy, and cardiovascular disease. The emphasis has been on the key outcomes and limitations of prior studies and on identifying potential future research directions and applications for high-Z NPs and spectral photon-counting CT imaging. The article concludes by discussing advancements aimed at improving the efficacy and safety of high-Z NPs for clinical use, and potential future developments in the field.