Theranostic materials are of great significance to a personalized precise medicine. However, conventional theranostic agents are mainly fabricated by combining presynthesized independent imaging probes and therapeutic agents, suffering from multiple synthesis procedures, poor morphological control, and time/reagent‐consuming process. Herein, iodinated polypyrrole (I‐PPy) nanoparticles are fabricated via a one‐step synthesis strategy combining chemical oxidation and iodination for computed tomography (CT) imaging‐guided photothermal therapy. Iodic acid with a high standard electrode potential enables the chemical oxidation polymerization of pyrrole monomers. Meanwhile, the iodination of PPy induced by the corresponding reduction product I2 takes place during the polymerization process to generate I‐PPy nanoparticles. The prepared I‐PPy nanoparticles possess a uniform size, excellent colloidal stability, intense near‐infrared absorption, strong X‐ray attenuation ability, and favorable biocompatibility. The as‐synthesized I‐PPy nanoparticles not only guarantee remarkable contrast‐enhanced CT imaging of blood pool and tumors, but also realize effective tumor suppression in vitro and in vivo by I‐PPy nanoparticles‐mediated CT imaging‐guided photothermal therapy. To the best of the authors' knowledge, it is the first time that multifunctional PPy nanoparticles are fabricated through a one‐step synthesis process. The proposed strategy opens up a new way for the fabrication of high‐performance theranostic agents via a one‐step strategy under mild conditions.