This study presents a system-level atmospheric water extraction (AWE) analysis using MIL-100 (Fe) as a representative material. This study considers a range of system features, including (i) modeling the isotherm across a wide temperature range based on the experimental data, (ii) conceptualizing process types and their operating conditions, (iii) analyzing the thermodynamics and economics, and (iv) optimizing the system operation under meteorological variations in temperature and humidity through two-stage stochastic programming. The swing capacity analysis revealed that a vacuum pressure below 0.1 bar and a temperature swing degree of 20–30 °C are necessary for feasible MIL-100 (Fe) AWE operation. Energy analysis shows that higher degrees of vacuum with moderate temperature swings result in lower energy consumption, requiring 4.6 and 1.6 MJ kgH2O−1 for thermal and electrical energy consumption. The estimated unit harvesting cost was 0.058 US$ kgH2O−1, with the potential for cost reduction through material and process development. We make contributions in several key areas: (i) facilitating the selection of optimal sites for pilot or commercial process implementation, (ii) offering insights into process design and operation, (iii) identifying and addressing potential bottlenecks for future process development, and (iv) providing a generalized platform for material screenings for comparative analysis.