Summary: Yolk-shell structure architecture is considered to be important in the fields that requires nanostructured designs such as energy storage systems. In particular, the internal and external structures, as well as compositions of yolk-shell materials, should be controllable in wide ranges to improve their properties for efficient applications in various fields. In this study, a new and general strategy to fabricate yolk-shell nanospheres with tunable compositions of yolk and shell parts under mild vacuum conditions is proposed. The melted metal salt is infiltrated in the void space of the hollow porous carbon nanospheres to form a yolk-shell structure under vacuum conditions, resulting in a yolk-shell structure with the configuration of a transition metal oxide (TMO)@, after a decomposition process under a vacuum. Yolk-shell nanospheres with configurations of ,@TMO-C and ,@TMO-C are also synthesized by controlling the vacuum degree for the infiltration of metal salt. Iron oxide, nickel oxide, and multicomponent materials are applied to confirm the applicability of the suggested method. This method facilitated in the tuning of the internal and external compositions was validated using various supporting data. The unique structured nanospheres with a configuration of FeO,@C showed an excellent lithium-ion storage performance.