The Rayleigh-Taylor (RT) interfacial instability has been attributed to physical phenomenon in a wide variety of macroscopic systems, including black holes, laser generated plasmas, and thick fluids. However, evidence for its existence in the nanoscale is lacking. Here we first show theoretically that this instability can occur in films with thickness negligible compared to the capillary length when they are heated rapidly inside a bulk fluid. Pressure gradients developed in the evaporated fluid region produce large forces causing the instability. Experiments were performed by melting Au films inside glycerol fluid by nanosecond laser pulses. The ensuing nanoparticles had highly monomodal size distributions. Importantly, the spacing of the nanoparticles was independent of the film thickness and could be tuned by the magnitude of the pressure gradients. Therefore, this instability can overcome some of the limitations of conventional thin self-organization techniques that rely on film thickness to control length scales.