Background: Septic shock, particularly due to ventilator-associated pneumonia (VAP), is a significant cause of mortality in critically ill patients. Traditional treatments include antimicrobial therapy, fluid resuscitation, and vasopressors. However, recent interest has emerged in using β-blockers to modulate the hyperadrenergic state seen in sepsis. β-blockers, like metoprolol, may improve cardiac efficiency, reduce myocardial oxygen demand, and ultimately enhance patient outcomes. Objective: This study aimed to assess the impact of administering intravenous metoprolol tartrate on the mortality rates of patients with septic shock due to VAP. Methods: This study employed a randomized clinical trial design within the Intensive Care Units of Alexandria Main University Hospital. A cohort of 100 patients diagnosed with septic shock due to ventilator-associated pneumonia (VAP) participated in the trial. Upon achieving hemodynamic stabilization, participants were randomly assigned to either receive standard care alone or standard care supplemented with intravenous metoprolol. Variables of interest included assessing 28-day mortality rates, duration of ICU stay and mechanical ventilation, reliance on intravenous fluids and vasopressors, acid-base balance, lactate levels, inflammatory markers, and mean arterial pressure (MAP). This comprehensive approach aimed to evaluate the impact of metoprolol on critical outcomes in this patient population. Results: The administration of intravenous metoprolol tartrate resulted in significant clinical benefits, including lower 28-day mortality rates (P = 0.013), shortened durations of ICU stay (P < 0.001), and reduced mechanical ventilation periods (P < 0.001). These outcomes were explained by the observed decreased reliance on intravenous fluids and vasopressors (P < 0.001), improved acid-base balance and lactate levels. The rapid reduction of inflammatory markers (P < 0.001) and the sustained improvement of MAP in the metoprolol group compared to the control group further contributed to the explication of these findings. Conclusion: Intravenous metoprolol tartrate effectively controlled inflammation, optimized hemodynamics, and improved patient outcomes compared to standard care, suggesting it as a beneficial adjunct in the management of septic shock. Trial registration: PACTR202404531355476. Keywords: Metoprolol; septic shock; ventilator-associated pneumonia; beta-blockers; mortality.