Background: Reaching the public health organizations targets of influenza vaccination in at-risk patient groups remains a challenge worldwide. Recognizing the relationship between the healthcare system characteristics and the economic environment of the population with vaccination uptake can be of great importance to improve. Methods: Several characteristics were correlated in this retrospective ecological study with data from 6.8 million citizens, 15,812 healthcare workers across 258 primary care health centers, and average income by area of the care center in Spain. Results: No correlation between HCW vaccination status and patient vaccination was found. A weak negative significant correlation between the size of the population the care center covers and their vaccination status did exist (6 mo.–59 yr.,r= 0.19,p= 0.002; 60–64 yr.,r= 0.23,p< 0.001; ≥65 yr.,r= 0.23,p≥ 0.001). The primary care centers with fewer HCWs had better uptake in the at-risk groups in the age groups of 60–64 yr. (r= 0.20,p= 0.002) and ≥65 (r= 0.023,p≥ 0.001). A negative correlation was found regarding workload in the 6 mo.–59 yr. age group (r= 0.18,p= 0.004), which showed the at-risk groups that lived in the most economically deprived areas were more likely to be vaccinated. Conclusions: This study reveals that the confounding variables that determine influenza vaccination in a population and in HCWs are complex. Future influenza campaigns should address these especially considering the possibility of combining influenza and SARS-CoV-2 vaccines each year.