Background: In 2017, in response to the alert issued by Santé publique France regarding the risk of an epidemic on the island of Mayotte due to the failure of maternal and child health services (PMI), the Director General of Health tasked the Indian Ocean Health Agency (ARS OI) with conducting a catch-up vaccination campaign targeting children under 6 years of age. Method: ARS OI submitted a request for support to Santé publique France to implement a catch-up vaccination program for children under 6 years of age in Mayotte. The three vaccines selected as priorities for this catch-up campaign were the hexavalent vaccine (diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), hepatitis B), the MMR vaccine (measles, mumps, rubella), and the pneumococcal vaccine. The vaccination campaign took place from May 22 to June 30, 2018; 39 temporary vaccination centers were set up successively across the territory; 110 public health reservists from Santé publique France were mobilized; 90,000 doses of vaccine were shipped to the island. The objective was to verify children’s vaccination status according to Mayotte’s 2018 vaccination schedule and to update it for the three vaccines offered. Public outreach was conducted through all media channels, including community media. The initiative relied on the involvement of local partners: the Departmental Council and the Mayotte Hospital Center (CHM), elected officials, associations, and religious mediators. Results: Of the 23,955 children who visited the vaccination centers, more than half required catch-up vaccinations for one to three of the recommended vaccines. Vaccination coverage (VC) was insufficient across all age groups. It reached alarming levels among children under 2 years of age (more than 80% of children were not up to date). VC rates for the first booster doses were insufficient for all antigens among children 15 months and older: 76% for DTP, 70% for Hib, 77% for hepatitis B, and less than 50% for pneumococcal. Only 70% of children 24 months and older had received both doses of MMR. BCG vaccination, primarily administered at the CHM at birth, was the only one to show satisfactory results: 89% of children had received one dose. Conclusion: In 2019, despite the catch-up vaccinations carried out during this campaign, the risk associated with vaccine-preventable diseases persists, and the functional revitalization of Mayotte’s PMI remains a major public health challenge.