Trehalose-6-phosphate phosphatase (TPP) modulates the Trehalose-6-phosphate–trehalose balance, a key regulatory node in plant carbon sensing and stress resilience. However, its functional roles in vegetative crops such as potato (Solanum tuberosum, St) remains poorly understood. Here, we conducted a genome-wide identification of the StTPP gene family and identified nine distinct loci distributed across five chromosomes. Phylogenetic analysis categorized these loci into three clades, supported by conserved HAD-box motifs and distinct exon–intron structures. Family expansion was driven by segmental duplication under purifying selection. In silico promoter analysis revealed cis-elements responsive to hormones, light, and stress, while network modeling identified 64 transcription factors potentially involved in regulating StTPP expression. A biphasic transcriptional response was observed in the salt-tolerant cultivar Xisen6: rapid induction of StTPP2/3/9 early in salt exposure, followed by late repression of most members. Subcellular localization assays indicated that StTPP3 is present in the nucleus and cytosol, suggesting multifunctional roles. These findings suggest that StTPPs integrate developmental and environmental signals, providing a molecular basis for improving potato stress tolerance and yield stability.