Background: The incidence and mortality rates of influenza and dengue have been high in most Asian countries. Vaccination is the one of the most important and successful public health measures in controlling many infectious diseases such as poliomyelitis, measles, and Japanese encephalitis. However, the etiological agents of these two diseases are RNA viruses involving different subtypes/serotypes with dynamic changes each year, posing greater challenges in future years. Methods and materials: Field epidemiology during outbreak periods provides the best chance in fully understanding dynamic changes of the studied virus and evaluating the impact of mismatched human influenza viruses. On the other hand, incidence and hospitalization rates, case fatality rates and seroepidemiological study of dengue are important in assessing public health needs and community effectiveness of vaccine as well as in finding target population to receive dengue vaccine. Results: We found that the higher isolation rate of seasonal influenza A (H3N2) and the circulating vaccine-mismatched human influenza viruses, the greater monthly P&I mortality in elderly, using a negative binomial model. Moreover, those years with high excess P&I mortality had the circulating virus strains with a lower amino acid identity percentages of HA1 protein with the vaccine strains. During 2009 pandemic influenza, one unique adaptive mutant at E374K of HA2 in A (H1N1/09) viruses evolved through the epidemic, emerged as a dominant strain at post-peak period, extended in areas with high population densities before mass immunization, persisted till ten months post-nationwide vaccination, and were finally fixed as herd immunity developed. Recently, different tetravalent dengue vaccines providing immunity against all four serotypes of dengue virus (DENV) have been developed to avoid antibody-dependent enhancement (ADE) from secondary DENV infection. The initial clinical trials in many cities of dengue-endemic countries did reduce the incidence and hospitalization rates of dengue. Conclusion: Weekly monitoring excess P&I mortality and evaluating laboratory-confirmed human influenza cases with/without receiving flu vaccines plus serological tests on antigenic variation can assure public health effectiveness of influenza vaccines. Once novel influenza virus emerges with worldwide spread, virological surveillance in high population-density areas can assess the virus with high epidemic potential. Furthermore, more immuno-epidemiological studies are needed for dengue in different settings.