Abstract: ^99mTc derived from ⁹⁹Mo, stands as the preeminent radiopharmaceutical employed extensively in medical diagnostics worldwide. Its current production mainly relies on some near-retirement nuclear reactors. Compared to reactors, particle accelerators have extremely low construction, operational, and maintenance costs, and their layouts are highly flexible. Given these circumstances, the production of ⁹⁹Mo/^99mTc by accelerator has become a research hotspot, with using electron-beam to irradiate ¹⁰⁰Mo to produce ⁹⁹Mo and proton-beam to irradiate ¹⁰⁰Mo to produce ^99mTc being the two most feasible methods. This article compares the advantages and disadvantages of two methods for preparing ⁹⁹Mo/^99mTc based on accelerators through experiments and Monte Carlo simulations. Direct production of ^99mTc by proton accelerators, the advantage is higher yield, but other Tc isotopes, especially ^99gTc, are produced alongside. In contrast, irradiating ¹⁰⁰Mo by electrons not only can produce high-purity ⁹⁹Mo with a simpler chemical separation process, but also make it suitable for preparing ⁹⁹Mo-^99mTc generators, which is relatively more advantageous.