<p>Persistent left superior vena cava is a congenital variation of the thoracic venous system. Although it is often asymptomatic, its presence can complicate procedures such as central venous access, cardiac device implantation, and cardiothoracic surgery. Reported prevalence data are inconsistent and predominantly derived from populations with underlying cardiac pathology. This study seeks to provide a robust, evidence-based estimate of the prevalence of persistent left superior vena cava in populations not preselected for congenital heart disease. Additionally, it aims to quantify its principal anatomical configurations, including the laterality of the superior vena cava and the presence or absence of a bridging brachiocephalic vein. A systematic search was conducted using PubMed, Google Scholar, Scopus, and Web of Science. Studies documenting the prevalence of persistent left superior vena cava in populations not selected on the basis of congenital heart disease criteria were included. Statistical analysis was carried out using random-effects meta-analytic models. Eighteen studies (<i>n</i> = 169,835 individuals) were included. The pooled prevalence of persistent left superior vena cava was 0.61% (95% CI: 0.38–0.89), with substantial heterogeneity across studies. Subgroup analysis demonstrated higher detection rates in cadaveric investigations (2.08%) compared with interventional studies (0.38%), likely reflecting differences in detection sensitivity. Bilateral superior vena cava was observed in 0.32% of the population, whereas isolated persistent left superior vena cava occurred in 0.10%. A bridging brachiocephalic vein was present in approximately 0.11% of the total population. Although uncommon, persistent left superior vena cava is a reproducible component of thoracic venous morphology with embryological significance. Awareness of its anatomical configurations is important in diagnostic and procedural contexts, especially when a dilated coronary sinus is observed during imaging.</p>