Five consecutive national vaccination plans (from 1999 to 2025) were revised, outlining their objectives, challenges, and results. Vaccination coverage for children consistently approached target levels, though regional differences emerged. In contrast, coverage for adolescents, the elderly, and vulnerable groups, consistently fell short of targets. While vaccination policies in Italy over the past 25 years were ambitious and well-planned, success was primarily limited to newborns immunization, thanks to effective organizational activities. Failure to achieve goals for other population groups was partly due to inconsistent implementation of regional vaccination prevention plans.