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Children with medical complexities, such as multi-system disorders and/or neurological impairments, often experience feeding difficulties and need enteral nutrition. They frequently have impaired motility and digestive–absorbing functions related to their underlying condition. If a cow’s milk allergy (CMA) occurs as a comorbidity, it is often misdiagnosed, due to the symptoms’ overlap. Many of the commercialized mixtures intended for enteral nutrition are composed of partially hydrolyzed cow’s milk proteins, which are not suitable for the treatment of CMA; thus, the exclusion of a concomitant CMA is mandatory in these patients for obtaining symptoms relief. In this review, we focus on the use of elemental and semi-elemental formulas in children with neurological diseases and in preterm infants as clinical “models” of medical complexity. In children with neurodisabilities, when gastrointestinal symptoms persist despite the use of specific enteral formula, or in cases of respiratory and/or dermatological symptoms, CMA should always be considered. If diagnosis is confirmed, only an extensively hydrolyzed or amino-acid based formula, or, as an alternative, extensively hydrolyzed nutritionally adequate formulas derived from rice or soy, should be used. Currently, enteral formulas tailored to the specific needs of preterm infants and children with neurological impairment presenting concomitant CMA have not been marketed yet. For the proper monitoring of the health status of patients with medical complexity, multidisciplinary evaluation and involvement of the nutritional team should be promoted.