Background: The aim of the study was to determine the predictors of meropenem treatment failure and mortality in the Intensive Care Unit (ICU). Methods: This was a retrospective study, involving sepsis and septic shock patients who were admitted to the ICU and received intravenous meropenem. Treatment failure is defined as evidence of non-resolved fever, non-reduced total white cell (TWC), non-reduced C-reactive protein (CRP), subsequent culture negative and death in ICU. Results: An Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of antibiotic treatment less than 5 days were associated with treatment failure with adjusted OR = 1.24 (95% CI: 1.15, 1.33; P < 0.001), OR = 65.43 (95% CI: 21.70, 197.23; P < 0.001). A higher risk of mortality was observed with higher APACHE and Sequential Organ Failure Assessment (SOFA) scores, initiating antibiotics > 72 h of sepsis, duration of antibiotic treatment less than 5 days and meropenem with renal adjustment dose with an adjusted OR = 1.21 (95% CI: 1.12, 1.30; P < 0.001), adjusted OR = 1.23 (95% CI: 1.08, 1.41; P < 0.001), adjusted OR = 6.38 (95% CI: 1.67, 24.50; P = 0.007), adjusted OR = 0.03 (95% CI: 0.01, 0.14; P < 0.001), adjusted OR = 0.30 (95% CI: 0.14, 0.64; P = 0.002). Conclusion: A total of 50 (14.12%) patients had a treatment failure with meropenem with 120 (48.02%) ICU mortality. The predictors of meropenem failure are higher APACHE score and shorter duration of meropenem treatment. The high APACHE, high SOFA score, initiating antibiotics more than 72 h of sepsis, shorter duration of treatment and meropenem with renal adjustment dose were predictors of mortality.