Vaccine hesitancy is a considerable obstacle to achieving vaccine protection worldwide. There needs to be more evidence-based research for interventions for vaccine hesitancy. Existing effectiveness evaluations are limited to one particular hypothesis, and no studies have compared the effectiveness of different interventions. A megastudy takes a large-scale, multi-intervention, uniform participant and the same evaluation criteria approach to evaluate many interventions simultaneously and find the most effective ones. Therefore, megastudies can help us find the most effective interventions for vaccine hesitancy. Additionally, considering the complex causes of vaccine hesitancy, we design interventions that involve social factors in megastudies. Lastly, quality control and justice are critical issues for megastudies in the future.