The development of new safe and effective contrast agents (CAs) is a crucial factor to increase the effectiveness of computed tomography (CT). For now, tantalum oxide-based nanoparticles (TaOx NPs) are among the most promising CAs for CT due to their superior properties: high X-ray attenuation coefficient, excellent biocompatibility, and easily modifiable surface chemistry. Compared to the commercially available analogs (iodine-based CAs), TaOx NPs provide better contrast performance, long-circulation, and high safety profiles (reduced exposure of X-rays and CA dosage). Among the investigated nanoparticulate CAs they afford higher cost-effectiveness (Au, Pt, Lu). TaOx NPs can also be easily modified to include other imaging or therapeutic modalities. This review aims to summarize the current state-of-the-art knowledge in the field of tantalum oxide-based CAs used for single or multimodal imaging and theranostic purposes. The design specification of TaOx NPs in terms of size, surface functionalization, composition, and their influence on the contrast performance, toxicity, and pharmacokinetics are discussed. Finally, the future opportunities and challenges of TaOx NPs used as CT CAs are addressed.