Diversities of salts formed by 5-sulfosalicylic acid (5-SSA) and isonicotinamide (INA) were obtained by mechanochemical grinding and from solution, including three polymorphs of (5-SSA-2H) − •(INA-H) + •H 2 O (1) (form 1a, form 1b, and form 1c), dehydration phase (5-SSA-2H) 2 − •(INA-H) 2 + (2), solvent phases (5-SSA-2H) − •(INA-H) + •MeOH (3) and (5-SSA-2H) 2 − •(INA-H) 2 + •H 2 O•MeOH (4), and stoichiometric form (5-SSA-2H) − • (INA-H) + •(INA) (5). The work studies not only the stabilities of the three polymorphs and the relationship between solvated 1 and desolvation phase 2 but also the interconversion of these crystalline phases. The dehydrated phase 2 and solvent phase 4 comprising two independent 5-SSA anions and two independent INA cations in the asymmetric unit form an individual ion pair and the corresponding hydrogen bonded networks. The solvent phase (5-SSA-2H) 2 − •(INA-H) 2 + •H 2 O•MeOH (4) shows the individual structural features of both (5-SSA-2H) − •(INA-H) + •H 2 O (1) and solvent phase (5-SSA-2H) − •(INA-H) + •MeOH (3). All seven salts build up layered structures but comprising a different hydrogen bonding network and can experience a reversible transformation. Quantum mechanics calculations are used to assess the stability of some of the crystalline phases under investigation. The example of salts of 5-SSA and INA comprising a diversity of solid forms reported here can be considered very rare, which has provided a good model for the insight into the structural transformation of materials of interest.