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Current fission-based methods of 99Mo production require single use uranium targets which leads to spent uranium waste. This waste could be reduced if a target is developed that does not require dissolution so that it can be reused for multiple production runs. MCNP6.2 was used to model reusable targets of 20% and 1% enrichment for activity produced, target efficiency and burnup. The 1% enriched target was found to be much more efficient but had a lower activity produced compared to the 20% enriched target. The ideal target design for 99Mo production that optimises efficiency and reusability and reduces the self-shielding effect of UO 2 was found to be a target that is made from 1% enriched UO 2 with density as high as allowable for sufficient yields, efficient 99Mo extraction and having an irradiation time of 5 days, with the target able to be re-irradiated and re-processed 2–4 times. • Current fission based manufacturing of 99Mo using uranium targets is based on target destruction. • Target destruction leads to increased radioactive waste volumes. • MCNP6 modelling of uranium targets show that higher density targets have more self-shielding effects and are less efficient. • Low density uranium targets with 5 days irradiation maximise 99Mo output and minimising radioactive waste. [ABSTRACT FROM AUTHOR]