With the aging of the population, the number of persons with dementia is expected to increase worldwide, making the establishment of preventive strategies for dementia an urgent issue. Several modifiable risk factors for dementia are known, and multidomain interventions that simultaneously intervene in multiple risks are becoming mainstream. This review aimed to overview multidomain intervention trials reported to date and ongoing trials regarding current challenges and future goals. Five multidomain intervention trials were published between 2015 and 2019, including the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), but consistent cognitive improvements were not evident. In the 2020s, seven of 10 trials reported the beneficial effects of multidomain interventions on cognitive outcomes in older adults. The other three trials failed to show significant cognitive improvement, partly due to the devastating impact of the coronavirus disease 2019 pandemic. Pre-specified subanalysis showed improvements in dementia risk factors, such as physical inactivity and nutritional status. These results suggest that multidomain interventions can protect against cognitive decline in older adults at risk for dementia. The World-Wide FINGERS Network was launched in 2017 to adapt and optimize findings to various geographic, cultural and economic settings, and to develop a global network of researchers working on preventing cognitive decline. Further development of the multidomain intervention is needed to enable social implementation considering the targets, delivery methods, scalability and cost-effectiveness. Hopefully, in the future, dementia will be treated similarly to cardiovascular disease in terms of early detection and early intervention. Geriatr Gerontol Int 2025; 25: 1015-1034.