We developed a multiscale model that integrates density functional theory (DFT), molecular dynamics (MD), and the finite difference method (FDM) to reflect the heterogeneous spatial distribution of the material ingredients on sub-10 nm photoresist (PR) pattern fabrication using extreme ultraviolet lithography (EUVL). It allowed the exploration of phototriggered chemical reactions at the molecular level, including photoacid generator (PAG) dissociation, acid diffusion-coupled deprotection, and solubility switching of individual polymer chains. To quantify the progress of the deprotection, a protection ratio of each pendant group was tracked to distinguish the dissoluble PR chains from the developer as the process time elapsed. Deprotection was shown to preferentially occur in the pendant group adjacent to the acid molecule (<0.74 nm), which determined the chemical gradient and solubility switching trend of the PR chains. Based on the full description of the phototriggered chemical reaction, the morphology of the PR line pattern was predicted after wiping out the dissoluble chains. We particularly examined the PAG loading effect (5.68−30.12 wt %) on the line edge roughness (LER) of the PR pattern and predicted the LER inversion phenomenon at the critical threshold PAG concentration, which qualitatively agreed with the experimental observations. Such a LER trend due to PAG loading was explained by the reciprocal interaction between the homogeneous packing of the acid from the dissoluble PR chains and the acid clustering behavior. The variation of the homogeneity of the deprotection in each pendant group was verified as a function of PAG concentration, which rationalized the existence of the reciprocal interaction.