The conventional fed-batch process characterized by a low titer currently challenges pharmaceutical development. Process optimization by applying a perfusion process in the pre-stage and subsequent production phase at a high seeding density (HSD) can meet this challenge. In this study, we employed a simplified approach based on measured experiments, namely segmented modeling, to systematically analyze an HSD fed-batch process compared to a standard process. A comparison indicated that the metabolic phases of HSD processes are not only shifted in time, but metabolite trends show an altered metabolism. In an extended study, we integrated the intracellular fluxes determined by a metabolic flux analysis into the segmented modeling approach. Compared to using only extracellular rates, similar phases are identified, and this highlights the reliability of phase identification modeling using extracellular rates only. Furthermore, the segmented linear regression approach is used to create a model that describes cellular behavior and that can be used to predict potential improvements in the feeding strategy and in harvest viability. Here, overfeeding was eliminated and a significantly higher titer was achieved. This work provides insights into the overall metabolic changes in the HSD process and paves the way towards the optimization of the feeding regime.