Intensive care patient nutritional therapy has been standardized by guidelines for decades. However, the same nutritional regimen to such a heterogeneous population seems a difficult task. These patients have various genotypes, numerous comorbidities, different severities and lengths of acute illness, and multiple interventions. Therefore, a new way of approaching the complexity of these patients is required, progressing from the whole body to compartments, organs, pericellular space, and cellular metabolism. We propose to untangle the complexity of intensive care unit patients by analyzing the complexity and deciding on the appropriate measures. These activities should aim towards personalized identification and prediction of adequate recovery measures, considering the generalization of guidelines based on the accumulated experience. Defining the specific nutrition supplement to affect various body niches could produce a significant contribution to the monitoring of nutritional complications, better understanding of the published nutritional interventions, and wise use of the nutritional tool in the complex patient.