Potato tubers can be dormant for 1–15 weeks after harvest, and the germination of tuber eye-buds is suppressed by cold. Genetic mechanisms regulating bud dormancy at low temperatures are not completely understood. We performed RNA-seq to compare gene expression in tubers after 0.5, 3.5, and 6.5 months of cold storage. Differentially expressed genes (DEGs) in non-dormant (3.5/6.5 months) vs dormant (0.5 months) tubers were associated with transcriptional and translational activation, cell growth, metabolism, hormonal signaling, meristem development, dormancy break, and reproduction, confirming the non-dormant state of the meristem in the middle of storage. DEGs encoding transcription factors (TFs) (CBF1, FLC, SVP, HY5, GI, CO, FT, SOC1, CDF1, POTM1) were associated with the regulation of dormancy, flowering, and tuberization. TF DEGs upregulated (78) or downregulated (224) over four times in non-dormant vs dormant tubers are considered potential coordinators of the endo- to non-dormancy transition and upcoming tuber sprouting during cold storage. RT-qPCR analysis of non-dormant and germinating buds revealed the upregulation of tuberigens (StSP3D, StFTL1-1, StFTL1-2), anti-tuberigens (StSP5G-like), and TF genes positively associated with tuberization or flowering/germination (StFDL1, StFDL, StCDF1, StCO-like). Our results should further investigation of the mechanisms underlying tuber meristem dormancy release and sprouting during long-term cold storage.