Background Tracheal intubation in critically sick patients presents a significant risk of complications attributable to variables such as respiratory failure, hemodynamic instability, and drug sensitivity. Present recommendations mostly depend on expert opinion and data from elective intubations, lacking substantial evidence from randomized controlled trials (RCTs) in critical care environments (ICU, ED, general wards). This systematic review sought to assess high-quality evidence-based methods for intubation in critically sick patients, concentrating on pharmacological agents, techniques, and equipment. Methods A thorough search of PubMed, BioMed Central, Embase, and the Cochrane Central Register of Clinical Trials found pertinent randomized controlled trials examining treatments aimed at enhancing the success rate and safety of tracheal intubation in critically sick patients. A meta-analysis was conducted when applicable. Results Intubation problems in critically sick patients vary from 4.2% to 39%. Pre-oxygenation by non-invasive ventilation (NIV) has shown enhanced effectiveness over conventional techniques in extending safe apnea duration and minimizing desaturation. Although high-flow nasal cannula (HFNC) enhanced comfort, its advantages for apneic oxygenation were restricted in this demographic. Etomidate and ketamine had equivalent safety and effectiveness as sedatives, whilst succinylcholine and rocuronium showed similar success rates as neuromuscular blocking drugs. The sniffing position outperformed the ramping position for laryngoscopy.