This study presents a comprehensive numerical investigation of the influence of gate oxide and buried oxide (BOX) materials on the electrothermal performance of two-dimensional MoS2-based metal–oxide–semiconductor (MOS) transistors. Particular attention is devoted to the analysis of the selfheating effect (SHE), subthreshold slope (SS), and drain-induced barrier lowering (DIBL), which are among the key performance-limiting factors in nanoscale devices. Al2O3 and HfO2 are considered as gate dielectric materials, while SiO2 and HfO2 are employed as buried oxide (BOX) materials. The dependences of the subthreshold slope and the lattice temperature at the channel center on the gate length are systematically evaluated for different combinations of gate oxide and BOX materials. A device structure with the channel fully covered by the gate dielectric is considered throughout the study. The simulation results demonstrate that the combination of an Al2O3 gate dielectric and a SiO2 BOX provides the lowest subthreshold slope, indicating superior electrostatic gate control. In contrast, employing HfO2 as both the gate dielectric and the BOX significantly mitigates the self-heating effect by improving thermal dissipation, thereby enhancing the thermal stability and reliability of the device. These findings provide valuable insights into dielectric engineering for the optimization of highperformance, low-power, and thermally reliable MoS2-based MOS transistors intended for future nanoelectronic applications.