Bimetallic nanostructures of specific compositions and enclosed by certain facets can significantly alter their physical and chemical properties and thus provide the opportunities to tailor them for particular electrochemical applications. Despite significant progress in recent years, it is still a grand challenge to control the spatial distribution of elements and surface structure of bimetallic nanoparticles. Thus, it remains very difficult to understand the properties of bimetallic nanoparticles, and even more challenging to overcome the formidable barriers to the rational design of bimetallic nanoparticles with the desired performance. This research focuses on the development of seed-mediated synthesis in solution aiming to precisely control the atomic arrangement in the bimetallic catalysts to establish the structure-composition-property relationship for electrocatalytic applications. In seed-mediated synthesis, the seeds can be preformed or in situ formed as a primary nanoscale substrate, followed by reducing secondary precursors to form bimetallic or multimetallic nanocatalysts. By controlling the shape of the seeds and reduction kinetics, well-defined bimetallic and multimetallic nanostructures can be obtained. In this work, CuPt and CuPtRu nanomaterials will be used as an example to demonstrate how changes of spatial atomic arrangement in the nanostructures influence their electrocatalytic properties for methanol oxidation. Fine tuning and mechanistic study of these synthetic strategies provide us fundamental understanding for precise control of bimetallic nanostructures to tackle problems in materials chemistry and open up the possibility for rational design and synthesis of future complex nanoarchitectures towards electrochemical applications.