This study aimed to investigate the heterogeneity of treatment effect for intra-aortic balloon pump (IABP) across various lactate trajectories in patients with acute myocardial infarction-related cardiogenic shock (AMICS) supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Retrospective data from the China Extracorporeal Life Support Registry included AMICS patients who received VA-ECMO. The latent class growth model was used to identify distinct lactate trajectories. The primary outcome was in-hospital mortality. Baseline characteristics and outcomes were compared across trajectory classes, and the heterogeneity of treatment effect for IABP was assessed. Among 1264 patients, three lactate trajectories were identified. Compared with Class 1, both Class 2 (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.54–2.67) and Class 3 (OR 3.99, 95% CI 2.77–5.78) had significantly higher in-hospital mortality. Moreover, heterogeneity of treatment effect across the classes was found. IABP use was associated with increased risks of in-hospital mortality and multiple complications (bleeding, renal, metabolic, and infection) in Class 1, whereas no associations were observed in Class 2 or Class 3, except for a higher risk of infection in Class 2. In summary, lactate trajectories can stratify mortality risk in AMICS patients receiving VA-ECMO support and reflect heterogeneous responses to IABP treatment.