Introduction Missed canal is one of the common reasons for nonsurgical endodontic retreatments. The missed canals were frequently associated with periapical pathology. The aim of this systematic review was to find the diagnostic accuracy of CBCT for detection of the second canal of the root canal system of permanent teeth. Materials and Methods The articles were selected from seven electronic databases according to selection criteria. All eligible studies were judged by the reviewers. The selected studies were checked with the QUADAS-2 tool for risk of bias and applicability concerns. Finally, 12 studies were selected for qualitative and quantitative analyses. The summary estimates of sensitivities and specificities and SROC curves were calculated and drawn by RevMan 5.3 and MetaDTA software. Results Summary estimates of CBCT for detection of second canal anatomy in permanent teeth were 94% sensitivity and 93.1% specificity. 96.6% sensitivity of MB2 was followed by 88.8% sensitivity of maxillary and mandibular premolars and 81% that of mandibular molars. The specificity of 97.6% for premolars was trialed by 85% specificity of mandibular molars and MB2. For permanent mandibular canines, 67% sensitivity and 100% specificity were estimated. CBCT showed more agreement with detecting the second canal with micro-CT, estimating 100% sensitivity and 95.6% specificity. The highest prevalence of the second canal comprised the highest sensitivity of 99.1% and lowest specificity of 77.5%. After the exclusion of case-control studies, a 3% drop of sensitivity from the summary estimate was observed. Multiple spectrum of the second canal had 8.6% higher sensitivity and 4.4% lower specificity than single spectrum. Conclusion CBCT is informative for detecting the second canal. Clinicians should keep in mind that the accuracy can vary in different types of teeth, with the prevalence of second canal across different populations, and with the spectrum of second canal anatomy in spite of the reviewers having postulated overestimation of the findings.