It is currently challenging to synthesis large, high-quality mica nanosheets to exploit nanoelectronics based on 2D mica. We carried out a first-principles investigation of the crystal and electronic structure as well as the interlayer interaction of mica intercalated with various organo-ammonium cations. The long-chain organo-ammonium cation intercalation expands interlayer spacing more efficiently, while the branched organo-ammonium cation intercalation is more effective in reducing exfoliation energy to facilitate exfoliation. Two exfoliation mechanisms are proposed as M1 (by increasing configurational entropy to destabilize interlayer structure, e.g., the interlayer spacing rises from 3.31 Å to 6.27 Å) and M2 (by increasing enthalpy to destroy interlayer structure, e.g., the exfoliation energy reduces from 2.51 eV to 1.13 eV). In addition, the intercalated mica shows remarkably narrowed bandgap attributed to ionic H-O bonds between mica tetrahedral sheets and organo-ammonium cations, which are dependent on the cation's degree of branching. Applying the energetic and structural analysis of organo-ammonium cation intercalated mica, our research furthers the understanding of cation intercalation and exfoliation of layer structured materials, opening the way for the effective massive production of nanosheets.