Nanocrystals of group 5 tetradymites M2X3 (where M = Bi and Sb, X = Se and Te) are of high technological relevance in modern topological nanoelectronics. However, there is a current lack of a systematic understanding to predict the preferred nanocrystal morphology in experiments where commonly-used equilibrium thermodynamic models appear to fail. In this work, using first-principles DFT calculations with a rationally-extended ab initio atomistic thermodynamics approach coupled to implicit solvation models and Gibbs-Wulff shape constructions, we demonstrate that this absence of predictive power stems from the limitation of equilibrium thermodynamics. By re-tracing and carefully addressing with a more realistic chemical potential definition, we illustrate this shortcoming can be overcome and afford a more rational route to size-engineer and shape-design highly-functional group 5 tetradymite nanoparticles for targeted applications.