Background: Acute poisoning represents a critical public health and medicolegal challenge in Egypt. The national toxicological profile is rapidly evolving and driven by complex sociodemographic determinants and the emergence of new psychoactive substances (NPS).

Methodology: A comprehensive narrative review of hospital, poison center, and medicolegal literature was conducted to evaluate the prevalence, intent, and analytical detection of major toxic agents across Egyptian governorates.

Results: The epidemiological burden exhibited distinct sociodemographic stratification. Pediatric exposures remain predominantly unintentional (68.5%), whereas adolescent cohorts demonstrate high rates of intentional self-harm (84.1%). A severe "dual burden" of toxicity exists. In rural governorates, highly lethal agrochemicals—particularly aluminum and zinc phosphides—dominate, accounting for up to 87% of suicidal fatalities in specific regional cohorts, with a marked female predominance (up to 59.7%). Conversely, urban cohorts face an escalating crisis of NPS misuse (e.g., "Strox" and "Voodoo") predominantly among young males. This condition is characterized by severe metabolic derangements, including respiratory acidosis (54.9%) and profound psychiatric comorbidities (91%). Furthermore, national case ascertainment is systematically constrained by diagnostic limitations.

Conclusion: Mitigating Egypt’s diverging threats of lethal agrochemicals and emerging NPS requires a paradigm shift from reactive care to integrated toxicological surveillance. Meaningful mortality reduction necessitates coordinated policy action: the phased restriction of highly hazardous pesticides, the establishment of a standardized national poisoning registry, and the implementation of tiered diagnostic stewardship utilizing mandated reflex liquid chromatography‒mass spectrometry (LC‒MS‒MS/MS).