Given　the　promise　of　energy　efficiency,　metal-organic　frameworks　(MOFs)　for　separation　applications　have　made　significant　progress　through　fine-tuning　of　their　pore　size　and　environment.　An　emerging　focus　in　the　field　is　the　one-step　separation　of　multicomponent　gas　mixtures.　Compared　with　binary　mixture　separation,　multicomponent　gas　mixtures　are　more　relevant　to　industrial　demand　and　their　separation　is　more　challenging.　In　this　review,　the　unique　features　of　multicomponent　mixture　separation　are　analyzed　and　new　strategies　for　such　a　challenging　task　critically　discussed.　The　separation　mechanisms　are　discussed　from　a　molecular　level　to　provide　insights　for　MOF　design.　To　conclude,　fundamental　questions　for　performance　optimization　have　been　proposed.　©　2023　Elsevier　Inc.