This paper examines the fire performance of uninsulated and uncoated restrained steel-concrete composite beams supplemented with externally prestressed strands through advanced numerical simulation. In this work, a sequentially coupled thermo-mechanical analysis is carried out using ABAQUS. This analysis utilizes a highly nonlinear three-dimensional finite element (FE) model that is specifically developed and validated using full-sized specimens tested in a companion fire testing program. The developed FE model accounts for nonlinearities arising from geometric features and material properties, as well as complexities resulting from prestressing systems, fire conditions, and mechanical loadings. Four factors are of interest to this work including effect of restraints (axial vs. rotational), degree of stiffness of restraints, the configuration of external prestressed tendons, and magnitude of applied loading. The outcome of this analysis demonstrates how the prestressing force in the external tendons is primarily governed by the magnitude of applied loading and experienced temperature level. Interestingly, these results also show that the stiffness of axial restraints has a minor influence on the failure of restrained and prestressed steel-concrete composite beams. When the axial restraint ratio does not exceed 0.5, the critical deflection of the composite beam is lower than that of the composite beam with a restraint ratio of 1.0.