Due to the threat of climate change, renewable feedstocks & alternative energy carriers are becoming more necessary than ever. One key vector is hydrogen, which can fulfil these roles and is a renewable resource when split from water using renewable electricity. Electrolyzers are often not designed for variable operation, such as power from sources like wind or solar. This work develops a framework to optimize the design and operation of a large-scale electrolyzer hub under variable power supply. The framework is a two-part optimization, where designs of repeated, modular units are optimized, then the entire system is optimized based on those modular units. The framework is tested using a case study of an electrolyzer hub powered by a Dutch wind farm to minimize the levelized cost of hydrogen. To understand how the optimal design changes, three power profiles are examined, including a steady power supply, a representative wind farm power supply, and the same wind farm power supply compressed in time. The work finds the compressed power profile uses PEM technology which can ramp up and down more quickly. The framework determines for this case study, pressurized alkaline electrolyzers with large stacks are the cheapest modular unit, and while a steady power profile resulted in the cheapest hydrogen, costing 4.73 €/kg, the typical wind power profile only raised the levelized cost by 2%–4.82 €/kg. This framework is useful for designing large-scale electrolysis plants and understanding the impact of specific design choices on the performance of a plant.