<p>Many people worldwide test negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B core antibody (HBcAb), posing potential clinical challenges of occult hepatitis B virus (HBV) infection (OBI), including viral reactivation and transmission. Understanding these scope of this issue is crucial, yet comprehensive data on OBI prevalence in this group is lacking. This systematic review and meta-analysis aimed to estimate the global prevalence of OBI among HBsAg-negative, HBcAb-positive individuals and explore factors related to variations in this prevalence. A comprehensive search of published studies was conducted using electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library Central, from January 1990 to January 12, 2025. The focus was on studies evaluating the prevalence of OBI in the hepatitis B core antibody (HBcAb)-positive general population. The search was limited to articles published in English. Among 48 studies with 21,783 participants, 44 studies (92%) used blood samples and 4 studies (8%) used liver tissue samples. The estimated OBI prevalence was 7% in HBcAb-positive and 2% in HBcAb-negative groups using blood samples, and 66% in HBcAb-positive and 0% in HBcAb-negative groups using liver tissue. OBI prevalence was higher in regions with high HBV endemicity compared to low-endemicity regions. The prevalence of OBI did not differ significantly between individuals with and without HBsAb within the HBcAb-positive group. OBI is found in a substantial proportion of HBsAg-negative/HBcAb-positive individuals, particularly when assessed in liver tissue, where prevalence may exceed 50%. Our findings indicate that the prevalence of OBI is higher in HBV endemic regions, and that HBsAb does not confer complete protection against OBI. Future research should aim to enhance OBI diagnostics and explore viral persistence mechanisms to improve clinical management and public health strategies.</p>