Meghalaya, a state in the northeastern region of India, had a markedly low vaccine uptake compared to the other states in the country when COVID-19 vaccines were being rolled out in 2021. This study aimed to characterize the distinct vaccine-hesitant subpopulations in healthcare and community settings in Meghalaya state in the early days of the vaccination program. We used data from a cross-sectional survey that was administered to 200 healthcare workers (HCWs) and 200 community members, who were a priori identified as 'vaccine-eligible' and 'vaccine-hesitant,' in Shillong city, Meghalaya, in May 2021. The questionnaire collected information on participants' sociodemographic characteristics, COVID-19 history, and presence of medical comorbidities. Participants were also asked to provide a dichotomous answer to a set of 19 questions, probing the reasons for their hesitancy towards COVID-19 vaccines. A multiple correspondence analysis, followed by an agglomerative hierarchical cluster analysis, was performed to identify the distinct clusters of vaccine-hesitant participants. We identified seven clusters: indecisive HCWs (n = 71), HCWs skeptical of COVID-19 and COVID-19 vaccines (n = 128), highly educated male tribal/clan leaders concerned about infertility and future pregnancies (n = 14), less educated adults influenced by leaders and family (n = 47), older adults worried about vaccine safety (n = 76), middle-aged adults without young children (n = 56), and highly educated ethnic/religious minorities with misinformation (n = 8). Across all the clusters, perceived logistical challenges associated with receiving the vaccine was identified as a common factor contributing to vaccine hesitancy. Our study findings provide valuable insights for local and state health authorities to effectively target distinct subgroups of vaccine-hesitant populations with tailored health messaging, and also call for a comprehensive approach to address the common drivers of vaccine hesitancy in communities with low vaccination rates.