Background: In the last years, a great effort has been made to unify different independent colorectal cancer (CRC) molecular classification systems into four consensus molecular subtypes (CMS). The four subtypes are found to be associated with distinct microenvironmental features and clinical outcome, although metabolic singularities are not well established. Metabolic dysregulation has been reported as a hallmark of CMS3, but metabolic heterogeneity among other subtypes has not been investigated. Here, taking into account the increasing evidence on the importance, for determining response to therapies, of the metabolic crosstalk between cancer cells, tumor microenvironment and immune cells, we investigated the metabolic singularities in the four CMS using a genetic immune-metabolic signature (IMMETCOLS). Conclusions: IMMETCOLS signature refines CMS prognosis in CRC patients and potentially allows specific metabolic interventions in CMS subtypes.