Abstract: This study establishes a multiphysics numerical model to investigate the evaporation dynamics of nanofluid droplets on heated substrates by employing the Arbitrary Lagrangian–Eulerian (ALE) method. The model fully couples internal and external fluid flow, heat transfer, and mass transport, while tracking nanoparticle motion within the droplet through a particle-tracing approach. Particular attention is given to the evolution of temperature fields, vapor concentration distributions, interfacial mass fluxes, and the trajectories of suspended nanoparticles during different evaporation stages. Simulation results demonstrate that the combined effects of substrate heating and surface evaporative cooling give rise to a Marangoni-driven vortex circulation inside the droplet. At the early stage, the flow is dominated by a single large-scale vortex that promotes efficient internal mixing. As the droplet geometry gradually flattens in the later stage, this circulation evolves into multiple smaller vortical structures. The appearance of such multi-vortex patterns introduces local perturbations in the interfacial temperature and evaporation flux, which further modulate the overall evaporation rate. Meanwhile, nanoparticles are strongly influenced by the flow field: some are advected towards the liquid–gas interface and then get trapped, while others are transported towards the substrate and eventually deposited, forming non-uniform deposition patterns. These findings reveal the coupled mechanism among temperature distribution, internal circulation, mass transport, and nanoparticle migration during nanofluid droplet evaporation. The results provide new physical insights into the interplay between thermocapillary convection and particle–flow interactions, which are often difficult to capture experimentally. Moreover, the study offers a theoretical foundation for optimizing the application of nanofluid working fluids in loop heat pipes and other thermal management systems in space environments, where efficient phase-change heat transfer and stable nanoparticle behavior are of critical importance.