Cofactors are external factors that can lower the threshold dose of an allergen and amplify the severity of allergic reactions, turning mild or moderate responses into severe anaphylaxis. These include exercise, nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, menstruation, and infections. Initially described in relation to food allergens and physical activity or NSAIDs, these reactions have been labeled under various terms, such as food-dependent exercise-induced anaphylaxis (FDEIA), wheat-dependent exercise-induced anaphylaxis (WDEIA), and food-dependent NSAID-induced anaphylaxis (FDNIA). However, cofactor-enhanced food allergy (CEFA), a recently proposed concept, serves as an umbrella term to encompass these conditions and is applied in this text for consistency. Pediatric cofactor-enhanced food anaphylaxis (PCEFA) is a rare but severe condition in which a food allergy becomes significantly more severe in the presence of one or more cofactors. Cofactors are documented in 14–18.3% of pediatric food anaphylactic reactions, however, the true burden is likely higher due to frequent underdiagnosis from variable and unpredictable presentations. Exercise and infections are the most common cofactors in PCEFA, while ω-5 gliadin is the predominant allergen. CEFA is frequently misdiagnosed as idiopathic anaphylaxis, exercise-induced anaphylaxis (EIA), or asthma when subtle or delayed food triggers go undetected. Some cases may represent high-threshold food allergies rather than true cofactor-dependent anaphylaxis, challenging conventional definitions. Research on cofactors in anaphylaxis is still in its early stages, with most studies focusing on adults. More research is needed to improve diagnostic accuracy and treatment strategies for pediatric cases.