This study evaluated the physicochemical and morphological properties of tooth enamel in patients with caries-predisposing SNPs (rs4694075 in AMBN and rs2337359 in TUFT1 genes), based on the DMFT index. We included 40 of 120 individuals (aged 19–43), collecting stimulated saliva and 58 healthy teeth extracted for orthodontic/surgical reasons. Saliva DNA was genotyped. Enamel properties were assessed using Vickers microhardness, deposition thickness, and calcium content. Genotype and allele frequencies aligned with the literature. The TUFT1C/C genotype subgroup showed a significantly higher DMFT index (p = 0.03) compared to the T/T genotype, while AMBN showed no such correlation. Calcium content, microhardness, and enamel thickness were similar across all polymorphic variants of both genes. A statistically significant correlation (p = 0.003) was found between reduced enamel calcium content and a higher DMFT index. Despite existing literature on the subject, the studied SNPs did not reflect any correlation with morphological or physicochemical changes in enamel. The above results suggest that genetic variability identifies patients classified by dentists as being at higher risk of caries, even though these patients follow a non-cariogenic diet and adhere to a hygiene regime. As no structural or physicochemical changes in the enamel of this group were observed, the potential cause may be disturbances in the remineralisation mechanisms or enamel surface properties that promote biofilm adhesion in polymorphic patients. Intensive tooth calcification control algorithms using LIF and RVG, as well as remineralisation cycles to increase hydroxyapatite saturation with calcium phosphates and bioadhesive fluoride delivery systems for long-term biofilm control, are used to more effectively prevent or slow down the progression of caries.