Soil salinity poses a significant environmental challenge for the growth and development of blueberries. However, the specific mechanisms by which blueberries respond to salt stress are still not fully understood. Here, we employed a comprehensive approach integrating physiological, metabolomic, and transcriptomic analyses to identify key metabolic pathways in blueberries under salt stress. Our findings indicate that blueberries primarily adapt to salt stress by modulating pathways associated with carbohydrate metabolism, organic acid metabolism, amino acid metabolism, and various organic compounds. Key metabolites involved in this response include sucrose, propionic acid, and palmitic acid. A total of 241 transcription factors were differentially expressed, with significant involvement from families such as AP2, Dof, GATA, WRKY, and TCP. Notably, the galactose metabolism pathway was associated with 5 DAMs and 24 DEGs, while the starch and sucrose metabolism pathway contained 5 DAMs and 23 DEGs, highlighting their crucial roles in mitigating salt stress. Overexpression of VcGolS3 in transgenic Arabidopsis conferred tolerance to salt and drought stresses, primarily evidenced by a significant increase in GolS enzyme activity and reduced ROS accumulation. This study provides valuable insights into the molecular mechanisms underlying the blueberry response to salt stress and lays the groundwork for breeding salt- and drought-tolerant blueberry varieties.