This　paper　aims　at　assessing　the　impact　of　removing　various　numbers　of　perimeter　columns　on　the　integrity　of　RC　flat　plate　substructures.　Compared　to　interior　columns,　those　at　the　corner　and　edge　positions　on　the　building　perimeter　are　more　likely　to　damage　by　accidental　and　abnormal　loads,　which　in　turn　may　cause　progressive　collapse　of　the　entire　structure.　Given　the　uncertainty　of　the　loading　events,　the　likelihood　of　multiple　perimeter　columns　being　simultaneously　destroyed　is　also　high.　However,　existing　research　has　primarily　focused　on　the　single　column　removal　cases.　To　address　this　research　limitation,　a　3D　high-fidelity　finite　element　model　of　a　flat　plate　substructure　with　a　missing　corner　column　(named　Model　C)　was　developed.　The　accuracy　of　the　model　was　validated　based　on　our　previous　experiment　of　the　same　substructure.　The　validated　model　was　subsequently　modified　to　cover　two　and　multiple　perimeter　column　removal　scenarios.　The　two　new　models　are　namely,　Model　C_1e　in　which　a　corner　column　and　an　adjacent　edge　column　were　damaged　and　Model　C_2e,　with　a　corner　column　and　two　adjacent　edge　columns　being　removed.　The　simulation　results　reveal　that　flexural　action　was　the　primary　load　resisting　mechanism　in　all　three　models.　The　load　carrying　capacity　with　three　column　removals　was　reduced　by　75.6%　compared　to　the　removal　of　a　single　corner　column.　Full-depth　cracks　were　found　at　the　cut-off　position　of　the　top　slab　rebars　for　the　columns　adjacent　to　the　removed　one(s).　In　Model　C　and　Model　C_2e,　cracks　exhibited　a　diagonal　axisymmetric　failure　pattern　of　the　corner　of　the　slab,　with　equal　load　transfer　to　two　adjacent　columns.　In　contrast,　Model　C_1e　exhibited　a　diagonal　non-axisymmetric　failure　pattern　of　the　slab　corner,　with　more　loads　being　transferred　to　the　adjacent　column　along　the　shorter　bay.　The　energy-based　dynamic　response　analyses　were　also　performed　to　obtain　the　Dynamic　Increase　Factor　(DIF)　for　the　substructure　models　under　different　column　removal　scenarios.　Based　on　the　nonlinear　regression　analysis,　the　DIFs　for　the　substructures　with　one　and　two　column　removals　were　found　to　be　ranged　between　1.22　and　1.51,　and　1.28-1.68,　respectively.