This study employs comprehensive clustering analysis to examine COVID-19 vaccine hesitancy and related socio-demographic factors across U.S. counties, using the collected and curated data from Johns Hopkins University. Utilizing K-Means and hierarchical clustering, we identify five distinct clusters characterized by varying levels of vaccine hesitancy, MMR vaccination coverage, population demographics, and political affiliations. Principal Component Analysis (PCA) was conducted to reduce dimensionality, and key variables were selected based on their contribution to cumulative explained variance. Our analysis reveals significant geographic and demographic patterns in vaccine hesitancy, providing valuable insights for public health strategies and future pandemic responses. Geospatial analysis highlights the distribution of clusters across the United States, indicating areas with high and low vaccine hesitancy. In addition, multiple regression analyses within each cluster identify key predictors of vaccine hesitancy in corresponding U.S. county clusters, emphasizing the importance of socio-economic and demographic factors. The findings underscore the need for targeted public health interventions and tailored communication strategies to address vaccine hesitancy across the United States and, potentially, across the globe.