The realization of nanoscale devices largely depends on our ability to control and manipulate interfacial interactions and, thus, understanding of the mechanisms of surface/interface instabilities. In this work, theoretically as well as technologically important and distinct two thermodynamic systems, which are exposed to (isobaric) and isolated from (isochoric) external body forces and surface tractions, are formulated by using irreversible thermodynamics in combination with the generalized variational method. The starting point for the present formulation closely follows up the Fowler and Guggenheim [Statistical Thermodynamics (University Press, Cambridge, 1952)] interpretation of the Planck inequality [Über Prinzip Vermehrung Entropie: Ann. Phys. Series 2(32), 462 (1887)] for isothermal reversible and irreversible (natural) infinitesimal changes in heterogeneous systems (multi-phase and multi-component). By combining this fundamental principle with the interlink between the dissipation function and global internal entropy production postulates, two distinct sets of governing equations for the surface drift-diffusion flux as well as the rate of evaporation/condensation and/or the growth/recrystallization of amorphous solid thin films are obtained for isochoric and isobaric systems. The role of Eshelby's energy-momentum tensor in the generalized potential for the interface displacement is found to differ (opposite in sign) for isochoric and isobaric systems. To demonstrate the importance of these sign conflicts, two sets of computer experiments are performed on isochoric and isobaric systems. They showed us that the elastic strain energy density contribution to the generalized driving force for surface drift-diffusion alone favoring flat and smooth surfaces in isobaric systems regardless of the sign of the uniaxial stress (healing), rather than causing the surface roughness and even catastrophic crack initiation as the case in internally strained isochoric systems. Computer simulations allowed us to track down the dynamical behavior of test modules by furnishing surface and strain energy variations, combined with the Global Helmholtz free change, which indicates the existence of two regimes: initial smooth surface undulations followed up by the rather chaotic crack formation and propagation stage at the middle of the thin film supported by the stiff substrate. In this study, we mainly focused on the development kinetics of “Stranski–Krastanow” island-type morphology, initiated by the nucleation route rather than the surface roughening scheme. The physicomathematical model, which is based on the irreversible thermodynamics treatment of surfaces and interfaces with singularities [T. O. Ogurtani, J. Chem. Phys. 124, 144706 (2006)], furnishes us to have autocontrol on otherwise free-motion of the triple junction contour line between the substrate and the droplet without presuming any equilibrium dihedral contact (wetting) angles at edges. We have also demonstrated the formation of the Stranski–Krastanow (SK)-type doublet islanding (quantum dots) as a stationary nonequilibrium state in an epitaxially strained thin flat droplet on a rigid substrate by introducing the wetting potential—invoked by the quantum confinement—into the scenario and carefully selecting the system parameters (size and shape) for the isochoric system represented by [Ge/Si (100)]. It has been also shown that on the contrary to common perceptions, the Stranski–Krastanow islands are in genuine stationary nonequilibrium states in the sense of Prigogine if one invokes proper free-moving boundary conditions at triple junctions deduced from the irreversible thermodynamics rather than ad hoc periodic or reflecting constrains at the edges.