Damp-heat gout (DHG) is a clinically recognized subtype of gout characterized by a specific syndrome in traditional Chinese medicine (TCM). However, its pathomechanism remains unclear, and there is a lack of quantifiable indicators for accurate clinical diagnosis and treatment. This study aimed to elucidate the pathological mechanisms underlying DHG and to establish a symptom-centered model for its diagnosis and treatment. A total of 136 participants, comprising healthy controls and diagnosed DHG patients, were recruited for the analysis. Utilizing serum metabolomics and proteomics methodologies, we identified 21 common pathways associated with DHG, highlighting four crucial pathways: bile secretion, cholesterol metabolism, purine metabolism, and arachidonic acid metabolism, which were found to correlate significantly with the primary symptoms of DHG. Additionally, six key biomarkers—hypoxanthine, prostaglandin E2, uric acid, deoxycholic acid, taurochenodeoxycholic acid, and bilirubin—were identified. These biomarkers demonstrated robust diagnostic potential, with AUC values of 0.987 in the discovery cohort and above 0.99 in the validation cohort. Furthermore, six potential protein therapeutic targets were identified, including ATP1A1, APRT, ANGPTL4, GLUT1, PTGES3, and LIPA. In conclusion, our study establishes a symptom-centered diagnostic and therapeutic model for DHG based on identified biomarkers. It also clarifies key metabolic pathways involved, paving the way for improved diagnosis and targeted treatment strategies in clinical management.