Understanding transformation pathway and mechanism in multiple-hydrates-system is essential for controlling hydrate forms in the manufacture. In this work, the investigation of thermodynamic stability, transformation pathway and mechanism of creatine phosphate sodium (CPS) hydrates was performed in the water–methanol solvent and vapor environment with different relative humidity (RH) via in-situ Raman, ATR-FTIR, DVS, PXRD, and SEM. Results show that, a novel ternary phase diagram was presented, where seven phase regions are included but without an anhydrate form’s region. The stability of CPS·2H2O, CPS·4.5H2O, and CPS·7H2O depends on the water activity and temperature. Phase transformation can be achieved between any two CPS hydrates in solution, influenced by water content, temperature and solid loading. Meanwhile, phase transformation in the vapor environment was found to carry on via three types of mechanism, solid-state transformation, solvent-mediated transformation, and solution-mediated transformation, the concepts of which were frequently confused before. This work elaborates on the concept and reveals the mechanism of solvent- and solution-mediated transformation, as well as provides guides for controlling hydrate forms in multiple-hydrates-system.