Stimulus-responsive organic room temperature phosphorescence (RTP) materials with luminescence properties changed with force, heat, etc., have drawn increasing attentions. Especially, the hydrostatic pressure effects on excited state properties of RTP molecules are conspicuous, corresponding theoretical investigations are highly desired. Herein, on the basis of density functional theory and time-dependent density functional theory, combined with the quantum mechanics/molecular mechanics and the thermal vibration correlation function methods, the influence of methyl substitution effect and hydrostatic pressure effect on the photophysical properties of five isomers is investigated theoretically. Results reveal that molecules with quasi-equatorial conformation have superior spin-orbit coupling (SOC) effects and more restricted geometric changes than molecules with quasi-axial conformation. In particular, the O-PTZ-H-1Me (eq) molecule has the minimum reorganization energy due to strong intermolecular interactions, significantly inhibits the non-radiative transition process, and exhibits a maximum intersystem crossing (ISC) rate for efficient triplet exciton generation. In addition, the quantum efficiency and lifetime are impressively improved by applying high hydrostatic pressure. Because of the small reorganization energy and SOC constant, the minimum non-radiative rate is achieved, resulting in a 64-fold (44.24%) increase in quantum efficiency and a 76-fold (21.12 ms) increase in lifetime compared to the unpressurized state.