Objective To systematically evaluate the effect of the timing of left ventricular (LV) unloading on the outcomes of patients with cardiogenic shock (CS) receiving extracorporeal membrane oxygenation (ECMO). MethodsA systematic literature search was conducted in PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed, and the VIP databases from their inception to February 2025. Literature screening was conducted according to predefined inclusion and exclusion criteria. Two researchers independently assessed the study quality and extracted the data. Patients were divided into an early unloading group and a late unloading group based on the timing of LV unloading. RevMan 5.4 software was used to perform the heterogeneity test and meta-analysis. Results A total of 8 studies involving 2 117 patients were included (1 338 in the early unloading group and 779 in the late unloading group). The meta-analysis showed no statistically significant differences between the two groups in the rates of successful ECMO weaning, in-hospital mortality, or 30-day all-cause mortality (all P>0.05). Compared with the late unloading group, the early unloading group had a lower risk of sepsis [RR=0.79, 95% CI (0.64, 0.96), P=0.02] and abdominal complications [RR=0.67, 95% CI (0.46, 0.96), P=0.03]. ConclusionCompared with late LV unloading, early LV unloading does not significantly improve the successful ECMO weaning rate or early survival. However, early LV unloading is associated with a reduced risk of sepsis and abdominal complications.