Public perception is one of the key determinants in the success of COVID-19 vaccination programs. Understanding the variables that influence perception can help guide effective public health strategies, especially in rural or underserved regions. This study aimed to examine the effect of demographic predictors, knowledge level, and family support on public perception of COVID-19 vaccination in the working area of the North Wakorumba Health Center, Indonesia. A cross-sectional analytical study was conducted involving 342 heads of households aged 18–59 years, selected through simple random sampling. Data were collected using structured questionnaires through home visits. Bivariate analysis was performed using the Chi-square test, and logistic regression was employed to identify significant predictors of perception at a 95% confidence level (α = 0.05). The results showed significant associations between perception and age (p = 0.012; OR = 5.186), education level (p = 0.031; OR = 1.870), and family support (p = 0.000; OR = 3.556). In contrast, knowledge, gender, and marital status did not show significant effects in multivariate analysis. Age, education, and family support were identified as significant factors influencing public perception of COVID-19 vaccination. Tailored health education and family-based interventions are essential to improve vaccine acceptance, especially among older adults and individuals with limited education or weak social support