The hygroscopic behavior of atmospheric aerosols is controlled by their chemical composition, which determines phase transitions, water uptake and physical state. Aerosol hydration influences particle size, mass, optical and chemical properties, making it a key process in atmospheric science. This study evaluates the performance of ISORROPIA 2.1, a thermodynamic equilibrium model, in predicting aerosol water uptake across a wide range of aerosol types, including indoor and outdoor (urban, extra-urban and marine) aerosols and deposits on electrical insulators. Inorganic composition was determined by ion chromatography, while deliquescence behavior was experimentally characterized using an Aerosol Exposure Chamber, providing a comprehensive dataset for model validation. ISORROPIA 2.1 accurately reproduces deliquescence relative humidity (DRH) and hygroscopic growth in sulfate–nitrate–ammonium dominated systems, with mean deviations of 4.3 ± 2.6 % RH for the onset of deliquescence (DRH_s) and 4.4 ± 3.2 % RH for completion (DRH_e). In contrast, ammonium-poor mixtures enriched in alkali and alkaline-earth ions (K⁺, Mg²⁺, Ca²⁺, Na⁺), including marine aerosol and insulator deposits, show non-physical humidification behavior characterized by discontinuous liquid–solid transitions. These anomalies arise from routine-selection instabilities in dust-rich regimes. Targeted code refinements improved model stability and water-uptake predictions, extending the applicability of ISORROPIA 2.1 to sulfate-poor, sodium- and crustal-rich systems. Overall, this work provides an experimental benchmark for aerosol thermodynamics, identifies the compositional limits of ISORROPIA 2.1 and broadens its applicability to complex inorganic aerosol mixtures.