BACKGROUND: Patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) face high mortality rates. Extracorporeal Membrane Oxygenation (ECMO) therapy offers critical support in these cases, yet identifying factors that influence patient outcomes is crucial for improving survival rates. METHODS: This retrospective study included 63 patients with AMI and CS who underwent ECMO therapy at our institution from January 2020 to December 2023. Patients were categorized into survivors (n = 33) and non-survivors (n = 30) based on 30-day outcomes. Data collected included demographics, clinical history, hemodynamic and biomarker parameters, and treatment details such as time from symptom onset to percutaneous coronary intervention (PCI) and the use of intra-aortic balloon pump (IABP). Logistic regression models and ROC curve analysis were used to evaluate the predictive value of various factors. RESULTS: Non-survivors had significantly higher arterial blood lactate levels (8.0 [6.2, 11.0] mmol/L vs. 4.8 [3.0, 8.5] mmol/L, p = 0.015) and required more intensive vasoactive support, as indicated by higher Vasoactive-Inotropic Scores (VIS) (130 [IQR: 105, 175] vs. 100 [IQR: 60, 115], p = 0.016). They also experienced longer delays from symptom onset to PCI (15.5 [IQR: 11.0, 20.5] hours vs. 9.5 [IQR: 7.0, 12.0] hours, p = 0.001). The prevalence of left main coronary artery disease (33.3% vs. 12.1%, p = 0.013) and triple vessel disease (36.7% vs. 9.1%, p = 0.002) was higher in non-survivors. ROC analysis identified arterial blood lactate (AUC = 0.6909), time from onset to PCI (AUC = 0.7667), and VIS (AUC = 0.703) as significant predictors of prognosis. Logistic regression showed that arterial blood lactate (OR = 1.884, p = 0.039), VIS (OR = 1.122, p = 0.033), and time from onset to PCI (OR = 108.271, p = 0.039) were significantly associated with worse outcomes. CONCLUSIONS: Elevated arterial blood lactate, prolonged time to PCI, and higher VIS could be important predictors of poor outcomes in AMI-CS patients undergoing ECMO therapy. Timely intervention, including rapid revascularization and effective management of metabolic disturbances, might be key to improving survival.