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Cervical cancer, closely linked to human papillomavirus (HPV) infection, is a major global health concern. Our study aims to fill the gap in understanding HPV vaccine awareness and acceptance in the Middle East, where national immunization programs are often lacking and cultural perceptions hinder acceptance. This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search across several databases was conducted on 5 September 2023. We included quantitative studies on HPV vaccine awareness and acceptance in Middle Eastern countries. Data extraction and quality assessment were conducted independently by multiple reviewers to ensure accuracy. Statistical analyses, including subgroup analyses, were performed using R to calculate pooled estimates, assess heterogeneity, and publication bias. We reviewed 159 articles from 15 Middle Eastern countries, focusing on 93,730 participants, predominantly female and healthcare workers. HPV vaccine awareness was found to be 41.7% (95% CI 37.4%-46.1%), with higher awareness among healthcare workers. The pooled acceptance rate was 45.6% (95% CI 41.3%-50.1%), with similar rates between healthcare and non-healthcare workers. Our study highlights the critical need for increased HPV vaccine awareness and acceptance in the Middle East, emphasizing the importance of integrating the vaccine into national immunization programs and addressing cultural and religious factors to improve public health outcomes.