The present work is part of a series of papers aiming at a thorough understanding of the thermodynamics of metabolism over a broad range of external conditions. The focus here is on the systematic study of solvation/hydration of a variety of fluids via an equation-of-state approach. This approach permits the study not only of the overall free energy, enthalpy or entropy of hydration but also their key components from cavitation, charging, and solute conformations/solvent restructuring contributions. These latter components shed light into the mechanism of hydration and contribute to our understanding of solvation phenomena at remote conditions of temperature and pressure. Hydrogen bonding is of central importance in this respect and is handled via the partial solvation parameter (PSP) approach. The developed solvation model is used for the estimation of the hydration quantities of key metabolites. The challenges and perspectives of this equation-of-state approach are critically discussed.