The optimal revascularization strategy in patients with multi-vessel disease (MVD) presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remains unclear. To investigate the comparative differences between culprit-only revascularization (COR) versus instant multi-vessel revascularization (IMVR) in AMI and CS. 13 studies were selected using MEDLINE, EMBASE and the CENTRAL (Inception - 31 November2017). Outcomes were assessed at short-term (in-hospital or ≤30 days duration) and long-term duration (≥6 months). Estimates were reported as random effects relative risk (RR) with 95% confidence interval (CI). In analysis of 7311 patients, COR significantly reduced the relative risk of short-term all-cause mortality (RR: 0.87; 95% CI, 0.77-0.97; p = 0.01, I2 = 50%) and renal failure (RR: 0.75; 95% CI, 0.61-0.94; p = 0.01, I2 = 7%) compared with IMVR. There were no significant differences between both the strategies in terms of reinfarction (RR: 1.25; 95% CI, 0.59-2.63; p = 0.56, I2 = 0%), major bleeding (RR: 0.88; 95% CI, 0.75-1.04; p = 0.14, I2 = 0%) and stroke (RR: 0.77; 95% CI, 0.50-1.17; p = 0.22, I2 = 0%) at short term duration. Similarly, no significant differences were observed between both groups regarding all-cause mortality (RR; 1.01; 95% CI, 0.85-1.20; p = 0.93, I2 = 61%) and reinfarction (RR: 0.71; 95% CI, 0.34-1.47; p = 0.35, I2 = 26%) at long term duration. In MVD patients presenting with AMI and CS, IMVR was comparable to COR in terms of all-cause mortality at long term follow up duration. These results are predominantly derived from observational data and more randomized controlled trials are required to validate this impression.