N-heterocyclic carbene (NHC) organocatalysis enables umpolung activation of enals to deliver chiral α,β-unsaturated acylazolium electrophiles, realizing a highly selective cascade Friedel-Crafts (F-C) alkylation/lactamization of 4-aminoindoles with regioselective C5-site functionalization and excellent enantioselectivity. Nevertheless, the underlying mechanism and origins of selectivities remain poorly understood. Herein, we report a comprehensive density functional theory (DFT) investigation to fully characterize the complete catalytic cycle of this cascade transformation. The computational results indicate that the electrophilic addition of 4-aminoindole to the α,β-unsaturated acylazolium intermediate governs the stereoselectivity and regioselectivity. Activation-strain model (ASM) and energy decomposition analysis (EDA) reveal that electrostatic interactions and dispersion forces constitute the dominant stabilizing factors for the energetically favorable S-configured transition state. For regioselectivity, projection of orbital coefficient vector (POCV) analysis quantifies intrinsic atomic reactivity of different indole carbon sites, verifying that higher atomic reactivity at C5 position accounts for the preferential C5-functionalization. This work establishes a full mechanistic map of NHC-catalyzed asymmetric F-C reaction of indole and provides quantitative theoretical tools (ASM, EDA, POCV) to predict and rationalize stereo- and regioselectivity, offering guidance for rational design of NHC catalytic systems for indole functionalization.