Background: Genetic and epigenetic alterations have significant impacts on the morphology of permanent mandibular premolars and molars. Geometric morphometry is a powerful technique, which can be utilized to identify specific landmarks that exhibit variation and that are associated with ancestry and dimorphism. Methods: The geometric and anatomic landmarks of mandibular premolars and molars were extracted from 3D digital replicas of diagnostic dental casts prepared for model analysis (n = 160). Tooth shape analysis was conducted using various techniques, including Procrustes superimposition, Procrustes ANOVA, discriminant function analysis, and the regression of shape over the centroid size. Results: Procrustes ANOVA showed that centroid size was not significantly different between the two sexes, but shape was significantly different in the two-cusp-type second premolars (p = 0.0035) and in the first/second molars (p < 0.001). The three-cusp type of the second premolars showed the highest degree of allometry, with 3.35%, followed by the mandibular second molars, with 3%, indicating that distal class types have a tendency to exhibit allometry. The distal and lingual components of the tooth showed more variability, and females tended to have sharper cusp configurations. Conclusions: This study shows how landmarks vary in permanent human post-canine dentition, a crucial finding for anatomic reconstruction and restorative dentistry. In particular, the molars and premolars of the mandible post-canine teeth are critical for achieving optimal masticatory efficiency and overall health. Additionally, a higher degree of allometry and the later formation of cusps correlate with greater shape variation, particularly on the distal and lingual sides. For precise restorative procedures, a thorough understanding of the anatomy of these teeth is required.