The pathophysiology of ST-elevated myocardial infarction (STEMI) extends beyond coronary artery occlusion to include microvascular and endothelial dysfunction, both of which critically influence outcomes. Endocan, a soluble dermatan sulfate proteoglycan secreted by endothelial cells, has emerged as a novel biomarker of endothelial activation and dysfunction. Recent studies suggest that elevated endocan levels may carry prognostic significance in patients with STEMI, particularly those undergoing percutaneous coronary intervention (PCI). A comprehensive search of PubMed, Cochrane Library, and Google Scholar was conducted to identify studies evaluating endocan as a prognostic biomarker in STEMI. Review articles, case reports, case series, and experimental studies were excluded. Seven clinical studies, comprising sample sizes ranging from 80 to 320 patients, met the inclusion criteria. Across these studies, endocan levels were analyzed in relation to established prognostic markers and clinical outcomes. Key findings demonstrated that higher endocan levels correlated with stress hyperglycemia (r = 0.21, p < 0.05), higher SYNTAX scores, and worse in-hospital outcomes. A cutoff value of 1.7 ng/mL predicted STEMI with 76.1% sensitivity and 73.6% specificity. Elevated endocan levels also showed positive correlations with the TIMI risk score, major adverse cardiovascular events (MACE), and were identified as independent predictors of incomplete ST-segment resolution (STR) (p = 0.044) and no-reflow phenomenon (NRP) (p < 0.001, OR = 2.39, 95% CI = 1.37–4.15). Collectively, the evidence indicates that endocan is strongly associated with endothelial dysfunction, MACE, NRP post-PCI, and impaired reperfusion. Moreover, traditional prognostic indices such as TIMI and SYNTAX scores appear to correlate with circulating endocan levels. However, variability in reported cutoff values across studies highlights the need for larger, multicenter trials with standardized endpoints to establish endocan’s diagnostic and prognostic utility in STEMI.