Background <p>The role of cardiopulmonary bypass (CPB) in surgery for tumor thrombi extending into the inferior vena cava (IVC) or right atrium in noncardiac malignancies remains controversial. We systematically compared perioperative mortality and complications between the CPB and non-CPB approaches and summarized findings on surgical techniques and patient selection.</p> Methods <p>We searched major databases for studies (2015–2025) reporting surgical resection of IVC or right atrial tumor thrombi in noncardiac malignancies stratified by CPB use. Twenty studies were included in the qualitative synthesis, and nine were included in the quantitative meta-analysis. Pooled perioperative mortality and complications were compared via random effects models. Heterogeneity and correlations between CPB use and mortality were assessed.</p> Results <p>Surgical approaches varied. CPB was typically reserved for extensive thrombus or right atrial involvement. The complication and recurrence rates were heterogeneous. In nine studies (800 patients), the pooled perioperative mortality rate was 9.2% (95% CI: 4.7–17.1%), with no significant difference between the CPB (10.3%) and non-CPB (7.8%) groups. High heterogeneity reflected differences in patient selection, tumor extent, and surgical technique. Qualitative synthesis indicated that CPB increased procedural complexity and risk but was utilized for more advanced disease. Recurrence and long-term outcomes have been inconsistently reported. Most studies were retrospective and at moderate to serious risk of bias.</p> Conclusion <p>Surgical management with or without CPB results in similar perioperative mortality rates. CPB is generally reserved for extensive thrombi, adding complexity and risk. Individualized, multidisciplinary planning is essential. Prospective studies are needed to refine patient selection and optimize surgical strategies in this challenging setting.</p>