Integrating　anammox　with　denitrifying　anaerobic　methane　oxidation　(DAMO)　in　the　membrane　biofilm　reactor　(MBfR)　is　a　promising　technology　capable　of　achieving　complete　nitrogen　removal　from　wastewater.　However,　it　remains　unknown　whether　reactor　configurations　featuring　longitudinal　gradients　parallel　to　the　membrane　surface　would　affect　the　performance　of　the　CH4-driven　MBfR.　To　this　end,　this　work　aims　to　study　the　impacts　of　longitudinal　heterogeneity　potentially　present　in　the　gas　and　liquid　phases　on　a　representative　CH4-driven　MBfR　performing　anammox/DAMO　by　applying　the　reported　modified　compartmental　modeling　approach.　Through　comparing　the　modeling　results　of　different　reactor　configurations,　this　work　not　only　offered　important　guidance　for　better　design,　operation　and　monitoring　of　the　CH4-driven　MBfR,　but　also　revealed　important　implications　for　prospective　related　modeling　research.　The　total　nitrogen　removal　efficiency　of　the　MBfR　at　non-excessive　CH4　supply　(e.g.,　surface　loading　of　≤0.064　g-COD　m−2　d−1　in　this　work)　was　found　to　be　insensitive　to　both　longitudinal　gradients　in　the　liquid　and　gas　phases.　Comparatively,　the　longitudinal　gradient　in　the　liquid　phase　led　to　distinct　longitudinal　biomass　stratification　and　therefore　played　an　influential　role　in　the　effective　CH4　utilization　efficiency,　which　was　also　related　to　the　extent　of　reactor　compartmentation　considered　in　modeling.　When　supplied　with　non-excessive　CH4,　the　MBfR　is　recommended　to　be　designed/operated　with　both　the　biofilm　reactor　and　the　membrane　lumen　as　plug　flow　reactors　(PFRs)　with　co-current　flow　of　wastewater　and　CH4,　which　could　mitigate　dissolved　CH4　discharge　in　the　effluent.　For　the　reactor　configurations　with　the　biofilm　reactor　designed/operated　as　a　PFR,　multi-spot　sampling　in　the　longitudinal　direction　is　needed　to　obtain　a　correct　representation　of　the　microbial　composition　of　the　MBfR.　©　2022　Elsevier　Ltd