Coherent topologically close-packed (TCP) nanoplates play a crucial role in enhancing the strength and creep resistance of magnesium alloys. However, the thermodynamic formation mechanisms of several metastable TCP nanoplates remain unclear, and the traditional trial-and-error methods impede the rapid discovery of novel TCP precipitate-strengthened Mg alloys. In this study, using density functional theory calculations to construct convex hull diagrams and evaluate thermodynamic stability, our results clarify that the metastable ${\beta }_2^{\mathrm{\prime }}$ nanoplates in Mg-Zn alloys adopt the Mg(Mg, Zn)₂ composition with excess Mg in precipitates. This finding demonstrates the metastable nature of the ${\beta }_2^{\mathrm{\prime }}$ phase and resolves the long-standing puzzle of its structural similarity to the equilibrium MgZn₂ phase in the Mg-Zn binary phase diagram. Moreover, by integrating the thermodynamic and kinetic conditions for TCP precipitation, we developed a two-step high-throughput screening strategy to systematically identify Mg alloy systems capable of forming stable TCP nanoplates. Our screenings identify 43 previously unreported TCP nanoplates and indicate that the current development of TCP-strengthened Mg alloys should mainly focus on the Mg-RE(Ca)-Al systems. These findings reveal the atomic-scale compositional complexity in TCP nanoplates and establish a theoretical foundation for designing creep-resistant Mg alloys containing TCP nanoplates.