The unanticipated emergence of the COVID-19 pandemic and the rapid spread of the mpox epidemic in 2022 and 2024 brought unforeseen challenges to public health. While distinct in nature, these outbreaks share some similarities and offer valuable insights into responding to novel virus dissemination in vulnerable populations. In light of these two experiences, we aim to discern the prioritization of medical countermeasures (MCM) among antivirals, antibodies, and vaccines. Comparative analysis of MCMs reveals that while antivirals serve essential roles as therapeutic tools, monoclonal antibodies can be used for both prevention and treatment, and vaccines remain of paramount importance for controlling epidemics as mass or targeted prophylaxis. Variability in production processes, administration methods, logistics, and costs distinguish these countermeasures. Vaccines, by inducing long-lasting immunity and ideally promoting herd effects, exhibit substantial advantages over other options. To enhance future pandemic readiness, proactive measures must include ready-to-use vaccine platforms with regulatory approval and manufacturing capacities, as well as prototype vaccines for representative pathogens and preexisting protocols to evaluate their efficacies and side effects. The comparison underscores the challenges of social acceptance and equity, particularly in vaccine production and distribution. As the world faces unknown agents, the three major types of MCMs do not have equal and symmetrical effects in terms of epidemic control. Thus, a vaccine-oriented strategy with a community-centered approach, proves essential for effective pandemic preparedness, encouraging continued innovation in vaccinology.