INTRODUCTION: Overexpression of tribbles homolog 3 (TRIB3) has been reported in various cancers, yet its clinical significance remains contentious. This study aims to elucidate the association between TRIB3 overexpression and the progression and prognosis of solid tumors. METHODS: A comprehensive analysis was conducted using data from published studies and The Cancer Genome Atlas (TCGA) up to May 2023. We evaluated the impact of high TRIB3 expression on tumor malignancy and survival outcomes across different cancer types. RESULTS: Seventeen studies met the inclusion criteria. Our findings revealed that TRIB3 overexpression is significantly associated with increased distant metastasis (OR = 4.01, 95% CI: 2.36-6.74,  < 0.001) and advanced histological stage (OR = 2.68, 95% CI: 1.50-4.78,  < 0.001). Additionally, high TRIB3 expression significantly elevated the risk of reduced overall survival (OS) in cancer patients (HR = 1.52, 95% CI: 1.05-2.20,  < 0.001), indicating a poor prognosis. Analyses of TCGA data among various prognostic indicators corroborated these findings. CONCLUSIONS: TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors. These results suggest that TRIB3 holds promise as a biomarker and therapeutic target in human cancers.