Background: Acute poisoning and drug overdose are important causes of emergency admissions, sometimes necessitate intensive care unit (ICU) support and mechanical ventilation (MV). The associated morbidity and mortality differ depending on the substance involved, patient comorbidities, and timeliness of care. This systematic review evaluates the clinical characteristics, indications for MV, and outcomes in ICU patients admitted due to poisoning or overdose. Methods: The literature search was conducted in (PubMed, ScienceDirect, and Google Scholar) after PRISMA guidelines. Studies included reported on adult patients with poisoning or drug overdose requiring MV. Outcomes include mortality, duration of MV, ICU length of stay, and associated complications. A total of nine studies were included in the qualitative analysis, with data extracted and synthesized. Results: The included studies showed on diverse populations, range from 48 to over 2.5 million patients. Poisoning was the predominant cause of ICU admission, with organophosphates and opioids are the most common toxic agents. MV was needed in 64% to 85% of cases. Predictors of MV and mortality included low Glasgow Coma Scale (GCS), high APACHE II or SOFA scores, delayed hospital presentation, co-ingestions, and psychiatric comorbidities. Mortality ranged from 2.8% to 33%, with higher rates in patients with pesticide or opioid overdose, mainly those with prolonged MV or delayed treatment. Conclusion: MV is important intervention to manage poisoning related ICU admissions. Early identification of high-risk patients and ventilation protocols improve outcomes.