BACKGROUND: Since December 2022, human cases of mpox in the Democratic Republic of the Congo (DRC) have risen at unprecedented rates. We identified a need for systematic mapping of the active research landscape and evidence, assessing their alignment with both local and global research priorities, to inform urgently needed research investments to support response efforts. METHODS: We conducted a mapping review of global research funding and international clinical trial registries and established a systematic rapid research needs appraisals platform to identify existing evidence gaps on mpox research. We analysed the alignment of these to established research categories and both local and globally identified mpox-specific research priorities. RESULTS: We identified 124 ongoing mpox research grants, 79 registered trials and 415 published studies. Most grants (85.0%, n = 105/124), clinical trials (49.3%, n = 39/79) and primary studies (57.7%, n = 205/355) were conducted in high-income countries, with most evidence published in response to the 2022 clade II global mpox outbreaks. Research funding has been focussed on vaccine and therapeutic pre-clinical development. Key gaps remain in both ongoing research and evidence relating to clinical characterisation among populations at risk, clinical trials on effective medical countermeasures specific to clade I, social sciences, health systems research, and healthcare and community protection. CONCLUSIONS: Our findings highlight persistent research gaps related to mpox clade Ib, particularly the limited knowledge on its characteristics and a lack of ongoing efforts to develop effective medical countermeasures, posing a risk to control efforts. Aligning research and investments to locally and globally identified research priorities and evidence gaps will help support national, regional and international responses to prevent transmission and improve outcomes.