Separation is one of the most energy-intensive processes in the chemical industry, and membrane-based separation technology contributes significantly to energy conservation and emission reduction. Additionally, metal-organic framework (MOF) materials have been widely investigated and have been found to have enormous potential in membrane separation due to their uniform pore size and high designability. Notably, pure MOF films and MOF mixed matrix membranes (MMMs) are the core of the “next generation” MOF materials. However, there are some tough issues with MOF-based membranes that affect separation performance. For pure MOF membranes, problems such as framework flexibility, defects, and grain orientation need to be addressed. Meanwhile, there still exist bottlenecks for MMMs such as MOF aggregation, plasticization and aging of the polymer matrix, poor interface compatibility, etc. Herein, corresponding methods are introduced to solve these problems, including inhibiting framework flexibility, regulating synthesis conditions, and enhancing the interaction between MOF and substrate. A series of high-quality MOF-based membranes have been obtained based on these techniques. Overall, these membranes revealed desired separation performance in both gas separation (e.g., CO2, H2, and olefin/paraffin) and liquid separation (e.g., water purification, organic solvent nanofiltration, and chiral separation).