Novel pulsed electric field (PEF) applications to modify the techno-functionality of biomacromolecules have recently emerged. Insights into the involved interplay of factor domains (electrical, flow, concentration, temperature) with respect to the treatment chamber locations, and into the scalability are lacking. Therefore, a parallel plate batch (0.8 mL) and a scaled up parallel plate continuous (50 mL, 0.83 mL s−1) setup were built and simulated to investigate these domains and resulting gradient interactions using liquid whey protein solutions (0.5% w/w). In both setups, protein agglomerations and aggregations were observed below 60 °C at the electrode boundary layers for pulses in the range of 2–2.5 kV cm−1, 10 μs, 40–350 Hz. The boundary layer is characterized by higher protein concentrations due to temperature- and pH-dependent migration trajectories, increased electrochemical reactivity (e.g., pH), and increased residence times due to the laminar flow or no flow conditions. Characterizing the domain interconnectivity led to effective scaling-up approaches of protein aggregations and insights into involved mechanisms.