Heat stress significantly affects livestock production, particularly in tropical regions where temperatures often exceed animals' comfort zones. This study investigates the molecular mechanisms of heat stress tolerance in Jamunapari goats (Capra hircus) through transcriptomic analysis, gene co-expression network construction, and hub gene identification. Female goats (1-2 years old) were monitored during high Thermal Humidity Index (THI) in June and normal THI in March. Based on heat tolerance and physiological parameters, goats were classified into Thermo-Neutral (TNG) and Heat-Stress (EHSG) groups. Differential gene expression analysis revealed 133 upregulated genes and 501 downregulated genes in the EHSG group. Upregulated pathways included NF-kappa B signaling, MAPK signaling, and cytokine-cytokine receptor interactions, while downregulated genes were linked to IL-17 signaling and platelet activation. Notably, the small heat shock proteins (CRYAB) and aquaporins (AQP11) were significantly downregulated. Weighted Gene Co-expression Network Analysis (WGCNA) identified key gene modules associated with Iberia Heat Tolerance Coefficient and respiration rate. Hub genes such as TUFM, TOMM40, BCSL1, VCL, VASP, ITGB, and VWF were critical for adaptation to heat stress. These findings enhance our understanding of heat stress resilience, offering potential targets for breeding programs aimed at improving livestock tolerance to heat stress in tropical environments.