Liquid-liquid phase separation (LLPS) has emerged as an intriguing phenomenon inside living cells. The phase-separated droplets, where specific biochemical events can take place and which also buffer cytosolic concentrations, are composed of weakly binding multivalent proteins or nucleic acids. Despite the explosion of this field of study, a general purpose quantitative principle to predict phase separation for multicomponent (“heterotypic”) binders has yet to emerge. In this study, we used non-spatial (NFSim) and spatial (SpringSaLaD) network-free rule-based modeling to determine the concentration threshold for LLPS as a function of molecular valencies. Remarkably, the simulations suggest that the phase separation behavior conforms to the solubility product constant (Ksp), familiar for ions in solution in equilibrium with solid salts: as long as the product of monomer concentrations exceeded the Ksp, the system showed phase separation - irrespective of the individual monomer concentrations. The solubility product constant decreases as the molecular valency of binding partners increases, shifting the concentration threshold to lower values. When we mixed molecules with different valencies, penta-valent and tri-valent, for example, Ksp followed an expression determined by ideal stoichiometries, similar to that of a mixed-valent salt like Al2(SO4)3. Spatial simulations revealed the importance of molecular flexibility and inter binding sites distance of the multivalent molecules. When the inter-site distances of a heterotypic tetravalent molecular pair are exactly matched, a prevalence of dimer (“dimeric trap”) was observed. A rigid molecular pair, with equal inter-site distances, produced this “dimeric trap” more prominently, while unequal inter-site distances disrupted the trap and formed large clusters that displayed a Ksp similar to that found in the non-spatial simulations. Thus our study establishes a general principle underlying the concentration threshold for phase separations, the Ksp, and how molecular structure can shape it. (Support: NIH grants R24GM137787 and R01GM132859)