The inland natural brine of Algerian chotts is known to contain considerable quantities of oceanic salts; hence, it becomes vital to estimate their mining and economic potential viability. This was done by carrying out an integrated geochemical simulation approach. It has been investigated how density and ionic composition change during isothermal evaporation experimentation (IEE) at 308.15°K. The crystallization path during the isothermal evaporation process is predicted using the Jänecke quinary diagram of the system Na+, K+, Mg2+//Cl–, and SO42–-H2O at 308.15°K and PHREEQC software (with Pitzer database). An integrated approach that is provided combines these two models with an experimental design. The nature and the crystallization sequence of the precipitated salts during the isothermal evaporation were determined by X-ray diffraction. The PHREEQC simulation, as well as Jänecke theoretical and experimental sequences, and the sequence provided by the real crystallization experiment all showed good agreement and confirmed the crystallization of halite, leonite, and sylvite minerals. At the end of the IEE, there was a minor deviation in the occurrence of epsomite in the recovered solids assemblage. The current study established that PHREEQC with Pitzer’s database and Jänecke quinary diagram are powerful tools recommended for the characterization and evaluation of unknown brines involving the Na+, K+, Mg2+//Cl–, and SO42–-H2O system at 308.15°K.