Background: This study aimed to evaluate the prevalence, morphology, and influencing factors of the second mesiobuccal (MB2) canal in maxillary molars and the middle-mesial canal in mandibular molars using cone-beam computed tomography (CBCT). Methods: A total of 146 CBCT scans acquired between 2023 and 2025 were retrospectively analyzed at the Oral Radiology Division, King Abdulaziz University Dental Hospital. Canal prevalence, morphometric dimensions, symmetry, and Vertucci configurations were recorded and correlated with age, sex, and voxel size. Results: MB2 canals were detected in 64.4% of maxillary first molars and 29.6% of second molars, while middle-mesial canals were found in 17.8% of mandibular first molars and 6.4% of second molars. Detection rates declined with increasing voxel size and patient age (p < 0.05). Bilateral symmetry was strong for MB2 (κ = 0.78) but moderate for mandibular canals (κ = 0.29). Vertucci Type I and II were most common in maxillary roots, and Type IV predominated in mandibular mesial roots. Conclusions: These findings confirm CBCT as a reliable tool for identifying complex canal systems and emphasize the importance of voxel resolution and anatomical understanding in enhancing endodontic diagnosis and treatment success.