This study aimed to explore the prevalence, antimicrobial resistance levels, and serotype distribution of S. pneumoniae in the Middle East region. We conducted a systematic literature review by searching several databases including PubMed, ISI Web of Science, Scopus, Google scholar through 2000 to 2017 by using the following keywords: “Streptococcus pneumoniae”, “pneumococcus”, “serotype”, “Antibiotic resistance,” and “Middle East “in combination with “OR” and “AND” Boolean Operators within Title/Abstract/Keywords fields. We used a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CIs) for binomial variables. All statistical analyses were done using STATA 12.0 (STATA Corp, College Station, TX). We found 73 articles appropriate, on the word of inclusion and exclusion criteria, for inclusion in this systematic review and meta-analysis. The result revealed that the pooled prevalence of S. pneumoniae carriage was 35% (95% CI: 26-44%). The most frequent pneumococcal serotypes were19, 19F, 6, 23 and 6A/B which were found in 19%,12%, 11%, 10% and 10% of isolates respectively. Pneumococcal resistance reported for azithromycin, cefaclor, clarithromycin, chloramphenicol, erythromycin, and tetracycline were 24%, 37%, 23%, 11%, 26%, and 29% respectively, while vancomycin resistance was not reported. The highest resistant prevalence was reported against co-trimoxazole (Trimethoprim/sulfamethoxazole). For this antibiotic, a pooled resistance prevalence of 43% was identified. The present review demonstrates that the prevalence of S. pneumoniae carriage was high in the Middle East region. Surveillance must be continued in this region to evaluate. The resistance pattern and serotype distribution.