Purpose Despite a 5-year survival rate of 20-45% for resectable colorectal liver metastasis (CRLM), prognostic tools are limited. There is a need for improved biomarkers to predict prognosis and treatment response. Extracellular vesicles (EVs) are endogenous nanoparticles that are potential biomarkers due to their role in metastases seeding. This systematic review evaluates the literature in relation to circulating EV biomarkers in CRLM. Methodology A systematic search across Medline, Embase, and Web of Science was undertaken, adhering to a strategy that included studies of any design in English, focusing on predictive markers from circulating EVs in human CRLM patients, from inception to 30 June 2024. The review was registered in the PROSPERO database (CRD42024606931). Results An initial search identified a total of 4300 studies. 564 studies met criteria to proceed to full-text review. Of these, the most common reason for exclusion was incorrect patient population (colorectal cancer without liver metastasis). After full-text review, a final total of seven studies met inclusion criteria. These studies highlighted the prognostic potential of three types of EV biomarkers: protein-based (three studies), micro-RNA-based (three studies), and total EV concentration (one study), all showing significant associations with survival outcomes in CRLM patients (p-values ranging from 0.0170 to <0.0001). Conclusions Circulating EVs are a promising prognostic biomarker candidate in patients with CRLM. This is a relatively new field of research and only a handful of studies have been published to date. Given these encouraging preliminary findings, we propose a prospective study to further explore and validate EV biomarkers in patients with CRLM.