Background/Objectives: Parenteral nutrition (PN) can be standardized or customized according to a patient’s individual needs, including clinical, metabolic, nutritional, and inflammatory conditions. The influence of inflammation on the indication of standard or customized PN for adolescents hospitalized in a quaternary hospital in the southeastern of Brazil was evaluated. Methods: A historical cohort study of 61 adolescents admitted to the hospital was conducted. Nutritional, clinical, and biochemical data from the first 7 days of PN use were analyzed. Elevated serum mineral and triglyceride levels, as well as renal or liver failure (grade III or IV), were considered unequivocal reasons for PN customization, while restoring energy-protein adequacy and low serum mineral levels were considered questionable reasons. Inflammatory status was analyzed during the study period. Results: A total of 128 PN solutions were prescribed, comprising 55 standardized and 73 customized. Overall, 40/61 patients required customized PN. The main reason for customization was to restore energy-protein adequacy (n = 48), while 24.7% (n = 18) of individualizations were for unequivocal reasons. Restoring energy-protein adequacy in the first 48 h was shown to have contributed to high transthyretin, which reduced the need for additional customized PN (r = −0.544; p = 0.044). A positive correlation was found between the total number of PN readjustments and C-Reactive Protein levels (r = 0.509; p = 0.044). Conclusions: Conditions such as malnutrition or an inflammatory state in adolescents presenting metabolic changes are indications for the use of customized PN.