Abstract Interfaces and interfacial mixing are omnipresent in fluids, plasmas, materials in vastly different environments. A thorough understanding of their fundamentals is essential in many areas of science, mathematics, and technology. This work focuses on the classical problem of stability of a phase boundary that is a subject to fluxes of heat and mass across it for non-ideal thermally conducting fluids. We develop a rigorous theory resolving challenges not addressed before, including boundary conditions for thermal heat flux, structure of perturbation waves, and dependence of waves coupling on system parameters in a broad range of conditions. We discover the novel class of fluid instabilities in the three regimes—advection, diffusion, and low Mach—with properties that were never earlier discussed and that are defined by the interplay of the thermal heat flux, thermal conductivity and destabilizing acceleration with the inertial stabilization. We reveal the parameter controlling transitions between the regimes through varying the initial conditions. We find that the interface stability is set primarily by the macroscopic inertial mechanism balancing the destabilizing acceleration. The thermal heat flux and the microscopic thermodynamics create vortical fields in the bulk. By linking micro to macro scales, the interface is the place where balances are achieved. Article highlights This work yields the general theory of interface dynamics in a broad range of conditions. The interplay is explored of inertial stabilization, destabilizing acceleration, thermal conductivity and heat flux. We discover that interface is the place where balances are achieved through linking micro to macro scales.