The synthetic antimicrobial agent Linezolid effectively penetrates many tissues and exhibits effectiveness against drug-resistant Gram-positive bacteria. This agent's pharmacokinetic qualities cast doubt on the need for intravenous treatment in cases of serious illness. For its time-dependent action to have an impact, serum levels must stay above the minimum inhibitory concentration throughout the dosage interval. According to our research, Linezolid infusions have been proposed to be given as continuous infusions to maintain adequate tissue and serum levels without trough concentration fluctuations. This will optimize the drug's effects and protect against toxicity and drug resistance. In critically ill individuals experiencing septic shock in the ICU, this study sought to validate the safety and efficacy of continuous Linezolid infusion in comparison to the conventional regimen. A prospective, randomized, controlled research involving 140 individuals suffering from septic shock who were older than 18 was carried out. Two groups of patients were randomly assigned. With an average treatment duration of 9.83 ± 2.537 in the intermittent infusion group and 7.39 ± 1.653 in the continuous infusion group, the first group obtained IV linezolid 600 mg twice daily as an intermittent infusion (II) over 60 minutes, whereas the second group obtained 300 mg IV as a loading dosage, and then continuous infusion of 900 mg/day in the first day and 1,200 mg/day in the subsequent days. There was a significantly high clinical cure and less ICU and hospital stay in the continuous infusion group (p < 0.001). Moreover, there was a lower incidence of developing thrombocytopenia in patients with renal impairment who got continuous infusion. Continuous infusion modality showed an advantage in terms of enhancing clinical efficacy in seriously ill cases with septic shock secondary to Gram-positive bacterial infection, especially in cases with renal impairment.