<p>Direct copper-to-copper bonding is increasingly employed in high-performance electronic devices, with nanotwinned (NT) copper emerging as a promising interconnect material due to its high strength and low electrical resistivity. This study investigates the coupled effects of temperature and strain rate on the macroscopic tensile response and microstructural stability of NT Cu over temperatures ranging from 25 to 200°C and strain rates from 1.6 × 10⁻⁵ to 5.4 × 10⁻⁴&#xa0;s⁻¹. The tensile and yield strength decrease by almost an order of magnitude with an increase in the temperature from 25 to 200°C. In contrast, at 25°C, increasing the strain rate by 1.5 orders of magnitude leads to a 30–40% rise in these strengths. The strain rate sensitivity (SRS) index <i>m</i> increased from ~ 0.014 at 25°C to ~ 0.213 at 200°C, whereas the apparent activation volume decreased from ~ 48 to ~ 18<i>b</i>^<i>3</i>. The simultaneous increase in <i>m</i> and decrease in activation volume suggest a transition in the dominant deformation mechanism from dislocation-dominated confined layer slip at 25°C toward dislocation climb at elevated temperatures. Microstructural characterization revealed temperature-induced grain growth, twin spacing coarsening, degradation of the (111) texture, and a reduction in dislocation density. To quantitatively capture the thermo-mechanical response, the experimental data were fitted to six constitutive models, among which the PB model demonstrated the highest predictive accuracy. These findings provide fundamental insight into the thermo-mechanical stability and deformation behavior of NT Cu for high-temperature interconnect applications.</p>