Objective: The aim of this study was to evaluate the accuracy of a combined approach based on an isotopological remeshing and statistical shape analysis (SSA) to capture key anatomical features of altered and intact premolars. Additionally, the study compares the capabilities of four Machine Learning (ML) algorithms in identifying or simulating tooth alterations. Methods: 113 premolar surfaces from a multicenter database were analyzed. These surfaces were processed using an isotopological remeshing method, followed by a SSA. Mean Euclidean distances between the initial and remeshed STL files were calculated to assess deviation in anatomical landmark positioning. Seven anatomical features were extracted from each tooth, and their correlations with shape modes and morphological characteristics were explored. Four ML algorithms, validated through three-fold cross-validation, were assessed for their ability to classify tooth types and alterations. Additionally, twenty intact teeth were altered and then reconstructed to verify the method's accuracy. Results: The first five modes encapsulated 76.1% of the total shape variability, with a mean landmark positioning deviation of 10.4 mu m (+/- 6.4). Significant correlations were found between shape modes and specific morphological features. The optimal ML algorithms demonstrated high accuracy (>83%) and precision (>86%). Simulations on intact teeth showed discrepancies in anatomical features below 3%. Conclusion: The combination of an isotopological remeshing with SSA showed good reliability in capturing key anatomical features of the tooth. Clinical significance: The encouraging performance of ML algorithms suggests a promising direction for supporting practitioners in diagnosing and planning treatments for patients with altered teeth, ultimately improving preventive care.