Toxicological investigations are often required by clinicians in comatose patients with suspected poisoning. However, the usefulness of toxicological analyses to support a diagnosis of acute poisoning is debated among clinicians and the interpretation of laboratory tests is challenging given the wide diversity of analytical techniques available. We report the case of an 8-year-old boy who was admitted to an intensive care unit with severe respiratory depression and neurological impairment. In order to formulate appropriate hypothesizes about the diagnosis and circumstances of intoxication, clinicians consulted toxicologists for a comprehensive toxicological screening. Routine blood immunoassays were negative for common toxicants but urine tests were positive for opiates. A general unknown screening using liquid and gas chromatography combined with mass spectrometry detection confirmed the presence of morphine, codeine and related glucuronides metabolites in plasma and urine. Subsequently, morphine and codeine were quantified in plasma samples by online-SPE-LC-MS-MS. In addition, analyses performed with GC-MS and LC-MSn identified compounds used as markers when profiling illicit heroin, namely noscapine, dextromethorphan and codeine. In conjunction with the patient's history, clinical picture and circumstances of intoxication, toxicological findings strongly suggested an acute pediatric opioid overdose as a collateral damage of parental heroin abuse in the home. This case highlights the significant contribution of toxicological investigations in sensitive legal cases and the critical role of communications between clinicians and toxicologists.