Purpose <p>Primary aldosteronism (PA), a common cause of secondary hypertension, requires precise localization and subtype differentiation for appropriate management. C-X-C chemokine receptor 4 (CXCR4) targeted PET-CT emerges as a promising non-invasive modality for evaluating PA. This study aims to assess its performance in three key areas: lateralizing aldosterone secretion, differentiating PA subtypes, and predicting surgical outcomes.</p> Methods <p>A systematic review and meta-analysis were performed, including studies that evaluated CXCR4-targeted PET-CT for PA diagnosis. Relevant literature was retrieved from PubMed, Embase, Scopus, Web of Science, WanFang, and CNKI (through January 10, 2025). Studies were included if they provided data on lateralization, subtype differentiation, or postoperative outcomes. Risk of bias was assessed using the QUADAS-2 tool. Pooled diagnostic metrics were calculated using random-effects models, with summary receiver operating characteristic curves analysis.</p> Results <p>Fourteen studies involving 1043 patients were included. CXCR4-targeted PET-CT demonstrated a pooled sensitivity of 74%[95%CI: 69-79%] and specificity of 85%[95%CI: 64-95%] for lateralizing aldosterone secretion. For subtype differentiation, sensitivity was 91%[95%CI: 82-96%] and specificity 92%[95%CI: 85-96%] in distinguishing aldosterone-producing adenoma from non- aldosterone-producing adenoma. In predicting postoperative outcomes, the sensitivity was 91%[95%CI: 84-95%], with accuracy of 77%[95%CI: 64-90%].</p> Conclusion <p>CXCR4-targeted PET-CT demonstrated clinical applications in: (1) accurately determining PA lateralization with high specificity; (2) reliably distinguishing PA subtypes; and (3) effectively predicting postoperative benefit. These findings support its potential use as an adjunctive tool in the clinical management of PA.</p> Systematic review registration no <p>CRD42025636887 (PROSPERO).</p>