X-rays are widely used in imaging applications such as diffraction imaging of crystals and medical imaging. In particular, X-ray computed tomography (CT) is a critical tool for clinical and disease diagnostics. The principle of conventional CT is based on X-ray attenuation caused by photoelectric absorption and scattering. In addition to conventional CT, a number of novel methodologies are presently under development, including state-of-the-art instrument technologies and chemical probes to fulfill diagnosis criteria. Among these novel methodologies, we have utilized hard X-ray-excited optical luminescence (hXEOL) as a new methodology to enhance the contrast of the image. Herein, we explored the possibility of hXEOL via iridium-doped polymer nanoparticles and biomolecule-directed metal clusters and propose it as a potential platform for new X-ray imaging.