Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major community health risk due to their resistance to last-line antibiotics. The Aim: This systematic review investigated the development and epidemiology of CRE in Saudi Arabia. Methods: Electronic databases were searched for studies published between 2019 and 2023, focusing on CRE in Saudi Arabia. A total of 21 studies met the inclusion criteria and were included in the review. Results: The results revealed a varying prevalence of CRE crossways different areas of Saudi Arabia, with rates ranging from 03% to 62.6%. Molecular mechanisms of resistance were primarily mediated by carbapenemases. Among the Enterobacteriaceae species, Acinetobacter baumannii has a prevalence of 23.21%, Klebsiella pneumoniae, has a prevalence of 17.22%. The prevalence of Enterobacterales, a wider category that includes various Enterobacteriaceae species, is reported to be 22.80%. Escherichia coli, has a prevalence of 23.08%. Proteus mirabilis, Klebsiella spp., Pseudomonas aeruginosa, Enterobacter cloacae, Morganella morganii, and Enterobacter aerogenes show higher prevalence rates of carbapenem resistance, ranging from 86.21% to 100%. These findings indicate a critical challenge in managing infections caused by these species, as carbapenems are often considered as last-resort antibiotics. The total prevalence of carbapenem resistance among the Enterobacteriaceae species is reported to be 22.23%. This highlights the significant burden of carbapenem resistance in Saudi Arabia and emphasizes the urgent need for effective strategies to prevent the spread of resistant strains and preserve the efficacy of carbapenem antibiotics. Conclusion and Recommendation: It is important to note that these results are subject to limitations, including variations in study design, sample size, and geographical representation.