Herein, we investigated to what extent molecular phenotypes of the systemic level (blood) and local (intestine) are associated with the performance of laying hens at 95 weeks of age. After the trial had run for 95 weeks, two performance groups were generated, i.e., egg production (PROD) and egg breaking strength (BS). A subset of 21 cages, 116 hens, was measured to indicate the metabolism and disease status. Additionally, a focus group (four cages) was made to perform molecular phenotyping in the intestine. A notifiable observation made during the post-mortem dissection was that approximately 12% of the birds at 95 weeks had developed certain aberrations and/or impairments (denoted as organ morbidity). At the systemic level, we observed five metabolites (γGT, triglycerides, HDL, glucose, and cholesterol) significantly associated to organ morbidity, and only two metabolites (urea and aspartate aminotransferase) to the performance phenotypes. At the local level, when comparing high PROD vs. low PROD, we observed differentially expressed genes involved in cell cycle processes and the extracellular matrix. When comparing high BS vs. low BS differentially, expressed genes were observed mainly involved in immune and cell cycle-related processes. This knowledge is crucial for developing novel strategies of keeping laying hens vital.