Nanoporous materials, such as metal-organic frameworks (MOFs), are renowned for their high selectivity as gas adsorbents due to their specific surface area, nanoporosity, and active surface chemistry. A significant challenge for their widespread application is reduced gas uptake in wet conditions, attributed to competitive adsorption between gas and water. Recent studies of gas adsorption in wet materials have typically used small amounts of powdered porous materials (in the milligram range) within very small reactors (1–5 mL). This leaves a gap in knowledge about gas adsorption behaviors in larger reactors and with increased MOF sample sizes (to the gram scale). Additionally, there has been a notable absence of experimental research on MOFs heavily saturated with water. In this study, we aimed to fill the gaps in our understanding of gas adsorption in wet conditions by measuring CH4 adsorption in MOFs. To do this, we used larger MOF samples (in grams) and a large-volume reactor. Our selection of commercially available MOFs, including HKUST-1, ZIF-8, MOF-303, and activated carbon, was based on their widespread application, available previous research, and differences in hydrophobicity. Using a volumetric approach, we measured high-pressure isotherms (at T = 274.15 K) to compare the moles of gas adsorbed under both dry and wet conditions across different MOFs and weights. The experimental results indicate that water decreases total CH4 adsorption in MOFs, with a more pronounced decrease in hydrophilic MOFs compared to hydrophobic ones at lower pressures. However, hydrophilic MOFs exhibited stepped isotherms at higher pressures, suggesting water converts to hydrate, positively impacting total gas uptake. In contrast, the hydrophobic ZIF-8 did not promote hydrate formation due to particle aggregation in the presence of water, leading to a loss of surface area and surface charge. This study highlights the additional challenges associated with hydrate-MOF synergy when experiments are scaled up and larger sample sizes are used. Future studies should consider using monolith or pellet forms of MOFs to address the limitations of powdered MOFs in scale-up studies.