The phase stability and microstructural evolution of nano-multilayer (NML) coatings during thermal treatments have attracted increasing attention in several technological fields, such as plasmonics, optics and joining. In the present study, the microstructural evolution of (Ag/AlN)_5nm/10nm NML coating upon heating in air and under vacuum was investigated by a combinatorial approach using SEM, TEM, XPS and XRD (both in the laboratory and at the synchrotron facility). Fast heating of the Ag/AlN NML in air up to 420 °C leads to an extensive migration of nano-confined Ag to the NML surface at temperatures as low as 200 °C, much below the Ag bulk melting point. Remarkably, the migration of Ag towards the surface is negligible for a similar heat treatment under vacuum, as well as for a thick Ag layer (i.e. in the absence of a nano-confinement of Ag). Outward migration of Ag is driven by the reduction of internal interfaces (i.e. nanograin- and phase-boundaries) in combination with the relaxation of thermally induced compressive stresses. The enhanced mobility of Ag in an O-rich atmosphere is attributed to the reduction of the activation energies for vacancy formation in the confined Ag nanolayers, as induced by the chemical interaction of inwardly diffusing O with Ag along Ag/AlN interfaces. The combined effects of nano-confinement, thermal stresses and an O-rich atmosphere in the Ag/AlN NML may be exploited for novel low-temperature joining applications.