Neutrophils are the most abundant human white blood cell and constitute a first line of defense in the innate immune response. Neutrophils are short-lived cells, and thus the impact of organismal aging on neutrophil biology, especially as a function of biological sex, remains poorly understood. We have generated a multi-omic resource of mouse primary bone marrow neutrophil from young and old female and male mice, at the transcriptomic, metabolomic and lipidomic levels. We identified widespread regulation of neutrophil ‘omics’ landscapes with organismal aging and biological sex. In addition, we leveraged this data to predict functional differences, including changes in neutrophil responses to activation signals. To date, this dataset represents the largest multi-omics resource for neutrophils across sex and ages. This resource identifies neutrophil characteristics which could be targeted to improve immune responses as a function of sex and/or age.