Background: The lack of seasonality in influenza epidemics in the tropics makes the application of well-established temperate zone national vaccination plans challenging. Objectives: We developed an individual-based simulation model to study optimal vaccination scheduling and assess costeffectiveness of these vaccination schedules in scenarios of no influenza seasonality and the seasonality regimes of Singapore, Taipei, and Tokyo. Methods: The simulation models heterogeneities in human contact networks, levels of protective antibodies following infection, the effectiveness of the influenza vaccine, and seasonality. Using a no intervention baseline, we consider 3 alternative vaccination strategies: (1) annual vaccination for a percentage of the elderly, (2) biannual vaccination for a percentage of the elderly, and (3) annual vaccination for all elderly and a fraction of the remaining population. We considered 5 vaccination uptake rates for each strategy and modeled the estimated costs, quality-adjusted life years, and incremental costeffectiveness ratios (ICERs), indicating the cost-effectiveness of each scenario. Results: In Singapore, annual vaccination for a proportion of elderly is largely cost-effective. However, with fixed uptake rates, partial biannual vaccination for the elderly yields a higher ICER than partial annual vaccination for the elderly, resulting in a cost-ineffective ICER. The most optimal strategy is the total vaccination of all the elderly and a proportion of individuals from other age groups, which results in a cost-saving ICER. This finding is consistent across different seasonality regimes. Conclusions: Tropical countries like Singapore can have comparably cost-effective vaccination strategies as found in countries with winter epidemics. The vaccination of all the elderly and a proportion of other age groups is the most cost-effective strategy, supporting the need for an extensive national influenza vaccination program.