During veno-arterial extracorporeal membrane oxygenation (VA-ECMO), the increase of left ventricular (LV) afterload can potentially increase the LV stress, exacerbate myocardial ischemia and delay recovery from cardiogenic shock (CS). Several strategies of LV unloading have been proposed. Systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement included adult patients from studies published between January 2000 and March 2019. The search was conducted through numerous databases. Overall, from 62 papers, 7581 patients were included, among whom 3337 (44.0%) received LV unloading concomitant to VA-ECMO. Overall, in-hospital mortality was 58.9% (4466/7581). A concomitant strategy of LV unloading as compared to ECMO alone was associated with 12% lower mortality risk (RR 0.88; 95% CI 0.82–0.93; p < 0.0001; I 2 = 40%) and 35% higher probability of weaning from ECMO (RR 1.35; 95% CI 1.21–1.51; p < 0.00001; I 2 = 38%). In an analysis stratified by setting, the highest mortality risk benefit was observed in case of acute myocardial infarction: RR 0.75; 95%CI 0.68–0.83; p < 0.0001; I 2 = 0%. There were no apparent differences between two techniques in terms of complications. In heterogeneous populations of critically ill adults in CS and supported with VA-ECMO, the adjunct of LV unloading is associated with lower early mortality and higher rate of weaning.