ABSTRACT Objective: To explore the correlation between the prognosis of patients with thyroid nodules and the characteristics of multimodal ultrasound imaging, Serological test indicator and TCM syndrome scores. Methods: A retrospective analysis was conducted on 200 patients with thyroid nodules collected between June 2023 and June 2024. Ultrasound elastography and color Doppler for nodule parameters serum free thyroxine (FT4), free triiodothyronine (FT3) level detection, and traditional Chinese medicine syndrome score evaluation based on internal Medicine of Traditional Chinese Medicine were performed. The associations between various indicators and prognostic outcomes were assessed using Spearman correlation analysis, binary logistic regression, and ROC curve analysis. Results: The poor prognosis group exhibited significantly higher proportions of irregular nodule morphology and blurred margins, along with significantly elevated values of elastic modulus (transverse plane average and longitudinal plane average), TCM syndrome scores, and FT4 levels (P<0.05). Spearman analysis revealed positive correlations between these indicators and poor prognosis (r=0.398-0.575, P<0.001). Logistic regression identified irregular morphology, blurred margins, TCM syndrome score, FT4, and transverse plane average as independent risk factors (P<0.05). ROC curve analysis demonstrated high diagnostic performance for transverse plane average (AUC=0.926), TCM syndrome score (AUC=0.901), and the combined predictive model (AUC=0.962). Conclusion: Multimodal ultrasound features, serum FT4 levels, and TCM syndrome scores demonstrated good predictive performance for thyroid nodule prognosis. The combined model significantly improved the predictive accuracy.