Objectives: This research aimed to determine if the same influenza vaccination strategies would have the same level of effectiveness when applied to two different US metropolitan areas, Miami and Seattle, where the composition of the population differs significantly in age distribution and household size distribution. Methods: We used an individual-based network modeling approach in which every pair of individuals connected in the social network is represented. Factorial design experiments were performed to estimate the impact of age-targeted vaccination strategies to control the transmission of a 'flu-like' virus. Results: The findings showed that: (1) age composition of the city matters in determining the effectiveness of a vaccination strategy and (2) vaccinating school children outperforms every other strategy. Conclusions: The most significant policy implication of this research is that there may not be a universal vaccination strategy that works across all cities with the same level of effectiveness. Secondly, given the important role of school children in the transmission of influenza, the US Government should consider the vaccination of school children a top priority. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.