After more than 22 months of the ongoing COVID-19 pandemic in the Region of the Americas, and COVID-19 cases and deaths have been reported from all 56 countries and territories in the Region of the Americas, health systems are still being challenged and routine immunization activities are still behind in most of countries. The pandemic has affected compliance with the vaccine-preventable diseases (VPDs) surveillance indicators. Furthermore, imposed restrictions on movement as well as concerns due to the pandemic have limited primary healthcare activities, including preventive services such as vaccination, with a consequent decline in the vaccination coverage and an increase of the susceptible population. In addition, the migration phenomena in the Region, the relaxing of public health and social measures, and the impact of COVID-19 on the capacity of the healthcare systems, have led to challenges. Therefore, the occurrence of new outbreaks of VPDs of varying magnitude in the Americas Region cannot be ruled out, and the regional risk remains assessed as Very High.