Background and Objectives: Despite substantial health benefits and prolific research efforts to demonstrate safety and increase uptake, vaccine hesitancy has increased dramatically. This study aimed to systematically analyze available literature on vaccine hesitancy in the United States and determine the rationale behind vaccine-hesitant parents and potential interventions. Methods: We conducted a literature search and identified 232 articles; we included 90 after screening. We pulled information from each article using standardized questions for “type of study,” “population,” “specific vaccine,” “reasons for hesitancy,” “hesitancy prevalence,” “attempt at change,” “results of intervention,” and “future interventions.” We created recurrent themes from the data and analyzed these themes via descriptive statistics. Results: Vaccine safety was the most commonly identified reason for vaccine hesitancy amongst studies (50%), followed by not enough information (30%), side effects (26%), low risk of disease (26%), social norms (22%), vaccine schedule (21%), not recommended by doctor (21%), efficacy (18%), cost/access (13%), sexual concerns (12%) and distrust of establishment (7%). Only 20% of papers documented an intervention, and <50% of these reported increased vaccination rates or intent. More research was the most commonly identified next step (49%). Conclusions: Despite large amounts of research on vaccination rates, patients are still reporting not enough information and safety as the most common reasons for vaccine hesitancy. Interventions were few and without promising results. More research was the most suggested intervention. Such research must address concerns of the vaccine-hesitant community, comparing risks and benefits of each vaccination in a longitudinal, coherent, and transparently unbiased fashion.