The article reports the synthesis and characterization of highly crystalline multimetallic nanoframes with three-dimensional electrocatalytic surfaces, specifically Pt3Ni nanoframes. These nanoframes are derived from the structural evolution of Pt-Ni bimetallic nanocrystals, starting from crystalline PtNi3 polyhedra. The transformation involves interior erosion, resulting in hollow Pt3Ni nanoframes with molecularly accessible surfaces. The edges of the initial PtNi3 polyhedra, which are Pt-rich, are maintained in the final nanoframes. The nanoframes exhibit enhanced oxygen reduction reaction (ORR) activity due to the formation of a nano-segregated Pt-Skin structure. The Pt3Ni nanoframes show over 36 and 22-fold improvements in mass and specific activities, respectively, compared to state-of-the-art Pt/C catalysts. The high catalytic activity and durability of the Pt3Ni nanoframes are attributed to their open framework structure, which allows access to both internal and external surfaces, and the optimal Pt-Skin thickness. The study also demonstrates the application of these nanoframes in the hydrogen evolution reaction (HER), further highlighting their potential in advanced electrocatalysis.The article reports the synthesis and characterization of highly crystalline multimetallic nanoframes with three-dimensional electrocatalytic surfaces, specifically Pt3Ni nanoframes. These nanoframes are derived from the structural evolution of Pt-Ni bimetallic nanocrystals, starting from crystalline PtNi3 polyhedra. The transformation involves interior erosion, resulting in hollow Pt3Ni nanoframes with molecularly accessible surfaces. The edges of the initial PtNi3 polyhedra, which are Pt-rich, are maintained in the final nanoframes. The nanoframes exhibit enhanced oxygen reduction reaction (ORR) activity due to the formation of a nano-segregated Pt-Skin structure. The Pt3Ni nanoframes show over 36 and 22-fold improvements in mass and specific activities, respectively, compared to state-of-the-art Pt/C catalysts. The high catalytic activity and durability of the Pt3Ni nanoframes are attributed to their open framework structure, which allows access to both internal and external surfaces, and the optimal Pt-Skin thickness. The study also demonstrates the application of these nanoframes in the hydrogen evolution reaction (HER), further highlighting their potential in advanced electrocatalysis.