Abiotic stresses adversely influence crop productivity and salt stress is one limiting factor. Plants need to evolve their defense mechanisms to survive in such fluctuating scenarios at either the biochemical, physiological, or molecular level. The analytical/critical investigations of cotton (Gossypium hirsutum) plants that involve looking into transcriptomic and metabolomic profiles could give a comprehensive picture of the response of the cotton plant to salt stress. This study was conducted on pre-treated cotton seeds by soaking them in a 3% sodium chloride (NaCl) solution at room temperature for 0.5, 1, and 1.5 h. In total, 3738 and 285 differentially expressed genes (DEGs) and metabolites, respectively, were discovered. The prominent DEGs included AtCCC1, EP1, NHE, AtpOMT, GAST1, CLC-c, ARP, AtKIN14, AtC3H2, COP9, AtHK-2, and EID1 to code for the regulation of seed growth, abscisic acid receptor PYR/PYL, a cellular response regarding stress tolerance (especially to salt) and germination, jasmonic acid, salicylic acid, and auxin-activated signaling pathways. A more significant amount of transcription factors, including the ethylene-responsive TFs ERF (205), bHLH (252), ZF-domains (167), bHLH (101), MYB (92), NAC (83), GATA (43), auxin-responsive proteins (30), MADs-box (23), bZIP (27), and HHO (13) were discovered in samples of NaCl-pretreated cotton seedlings under different treatments. The functional annotations of DEGs exposed their important roles in regulating different phytohormones and signal-transduction-mediated pathways in salt-treated seeds. The metabolites analysis revealed differential accumulation of flavonols, phenolic acid, amino acids, and derivatives in seedling samples treated for 0.5 h with NaCl. The conjoint analysis that showed most of the DEGs were associated with the production and regulation of glucose-1-phosphate, uridine 5′-diphospho-D-glucose, and 2-deoxyribose 1-phosphate under salt stress conditions. These results indicated positive effects of NaCl 0.5 h treatments on seedlings’ germination and growth, seemingly by activating specific growth-promoting enzymes and metabolites to alleviate adverse effects of salt stress. Hence, seed pre-treatment with NaCl can be beneficial in future cotton management and breeding programs to enhance growth and development under salt stress.