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Despite the availability and benefits of the Human papillomavirus (HPV) vaccine, parental acceptance remains low in the eastern mediterranean region (EMR). Therefore, this meta-analysis aimed to estimate the pooled proportion of parental uptake and willingness to vaccinate their children with the HPV vaccine and their determinants in the EMR. We searched PubMed Central, PubMed Medline, Scopus, Web of Science, ProQuest, Google Scholar, and medRxiv according to PRISMA guidelines until the 5th of April 2024. We included all papers discussing parental uptake and willingness to vaccinate their children with the HPV vaccine in EMR without time or language limitations. The study risk of bias was assessed using the Newcastle–Ottawa Scale quality assessment tool. We pooled data using the random effect model. Leave one sensitivity analysis, subgroup analysis, and meta-regression were used to address heterogeneity. Out of 1551 screened studies, thirty-three studies of 18,455 parents from 12 countries fully met the inclusion criteria and were eligible for meta-analysis. The pooled proportion of parental willingness for future HPV vaccination, based on 32 studies involving 17,815 parents was 61 % (95 % CI: 54–68 %, I2 = 99 %). Using meta-regression, the proportion of working parents, study quality, and geographical region explained approximately 52.46% of the observed heterogeneity. In contrast, based on 9 studies involving 5029 parents, the pooled proportion of parental uptake was 7 % (95 % CI: 5–10 %, I2 = 91 %). Using meta-regression, study quality and geographical region explained 71.42% of the observed heterogeneity. Despite the high parental willingness for HPV vaccination, the uptake of the vaccine in EMR remains critically suboptimal and far behind the goal of the World Health Organization's cervical cancer elimination strategy. Urgent interventions are needed, including adding the vaccine to the national vaccination programs (NVPs) and tailoring parents–targeted awareness campaigns to improve knowledge and address barriers to vaccine uptake.