Trace elements are key factors involved in a wide range of roles, from immune response, to hematopoiesis, neurocognitive function, components of antioxidant enzymes, metabolic components, and many others. The pathophysiology of trace element deficiency is complex, and involves—beyond reduced absorptive surface and malabsorption—impaired motility, altered digestive secretions, dysbiosis, and altered hormonal modulation. The evaluation of trace element deficits involves both following clinical features of deficiencies and measuring level in biological samples, mainly serum or plasma. During parenteral nutrition phase, monitoring of trace elements should be more frequent, while after weaning off parenteral nutrition, the monitoring should be adjusted based on patients’ evolution. Proper monitoring is the mainstay for an optimum supplementation strategy while avoiding excess levels with potential toxicity.