Design and preparation of mixed-matrix membranes (MMMs) with minimum defects and high performance for desired gas separations is still challenging as it depends on a variety of MMM synthesis parameters. In this study, 6FDA-DAM:DABA based MMMs using MOF-808 as filler were prepared to examine the impact of multiple variables on the preparation process of MMMs, including variation in polymer concentration, filler loading, volume of solution cast per membrane area, solvent type used and solvent evaporation rate, and to identify their impact on the CO2/CH4 separation performance of these membranes. Solvent evaporation rate proved to be the most critical synthesis parameter, directly influencing the performance and visual appearance of the membranes. Although less dominantly influencing the MMM performance, polymer concentration and solution volume also had an important role via control over the casting solution viscosity, particle agglomeration, and particle settling rate. Among all solvents studied, MMMs prepared with chloroform led to the best performance for this polymer-filler system. Chloroform-based MMMs containing 10 and 30 wt.% MOF-808 showed 73% and 62% increase in CO2 permeability, respectively, without a decrease in separation factor compared to unfilled membranes. The results indicate that enhanced gas separation performance of MMMs strongly depends on the cumulative effect of various synthesis parameters rather than individual impact, thus requiring a system-specific design and optimization.