Abstract: ^99mTc, as the daughter of ⁹⁹Mo, is the most important medical radioisotope in nuclear medicine. ⁹⁹Mo is usually extracted from fission products of uranium235. Due to the restriction of treaty on the NonProliferation of Nuclear Weapons (NPT) for high enriched uranium (HEU, higher than 90% ²³⁵U enrichment that is usually 93%), it will be the trend to use low enriched uranium (LEU, less than 20% ²³⁵U enrichment that is usually 19.75%) targets for medical ⁹⁹Mo production. Up to date, South Africa, Australia, Belgium and Netherland had completed the conversion from HEU to LEU technology. In this paper, based on medical application and market demand of ⁹⁹Mo, opportunity and challenge of ⁹⁹Mo production with LEU targets were analyzed. Non-fission ⁹⁹Mo can be produced at a large scale by neutron irradiating ⁹⁸Mo target in reactor, while the fabrication technology for ⁹⁹Mo-^99mTc generator with low specific activity of ⁹⁹Mo has not been broken through, which indicates little possibility of replacement of fission ⁹⁹Mo by non-fission ⁹⁹Mo. For the LEU technology itself, emphasis should be put on fabrication of LEU target, high efficiency of ⁹⁹Mo seperation from LEU target.