Background: Acute poisoning in children is regarded as a severe problem that frequently results in morbidity and death worldwide. Toxic coma is a potentially fatal illness, representing a great challenge for toxicologists. Aim of the work: The study aimed to describe the pattern and outcome of acute poisoning-induced coma among preschool children, as well as to compare modified Acute Physiology and Chronic Health Evaluation II (modified APACHE II), the Mainz Emergency Evaluation System (MEES), and the Glasgow Coma Scale (GCS) in mortality prediction. Patients and methods: A retrospective cross-sectional study was conducted on preschool children with acute poisoning-induced coma admitted to the ICU of PCC-ASUH from June 2022 to December 2023. Results: The study included seventy-four patients, 11 of whom were non-survivors. Most of the patients were male and two years old. Cannabis, clozapine, and hydrocarbons were the most frequent toxic agents inducing coma in preschool children. The mortality rate was 14.9%. The best cut-off points for predicting mortality in modified APACHE II, MEES, and GCS scores were > 9, ≤ 18, and ≤ 9, with specificities of 90.4%, 93.6%, and 96.8%, respectively, and sensitivities of 100%. The MEES and GCS scores had the highest AUC (0.986), followed by the modified APACHE II (0.978). There was no statistically significant difference among the scores' AUCs. Conclusion: The modified APACHE II, MEES, and GCS scores were significant predictors of mortality in preschool children with acute poisoning-induced coma. GCS is easier to apply than other scores and is recommended for use.