In order to determine the possibilities to control the chemical configuration of bimetallic nanoparticles, we have considered CuAg nanoparticles synthesized by a physical route as a model in this study. The synthesis was made by pulsed laser deposition under ultra-high vacuum conditions, via a sequential deposition procedure. We show that the temperature of the substrate and the absolute quantity of Ag in a particle are the main parameters that drive the chemical configuration. To explain the transition from a core–shell configuration to a Janus configuration as a function of Ag quantity, we have conducted density-functional theory calculations and atomistic molecular dynamics simulations to investigate the stability of this system. The results are presented together with the experimental observations.