Through-silicon via (TSV) technology has the potential to overcome existing limitations of miniaturization and to increase the performance of electronic devices. However, the interface between the solder and copper via has introduced some reliability issues. In contrast to conventional solder-based interconnects, Cu-Cu direct thermo-compression bonding (CuDB) presents an alternative to enable 3D package integration. Direct copper bonding has many advantages, including a reduction in soldering process steps, fine interconnect density, enhanced thermal conductivity, and less concern about intermetallic compounds (IMC) formation. To study the reliability of a device using direct copper bonding, a parametric study based on thermo-mechanical simulations is conducted to evaluate the design of a 3D test vehicle with direct copper bonding. Sub-modeling and lumped parameter methods are employed to account for the large differences in scale from the TSV level to the package level. Thermal simulations are performed for various package and heat source configurations using both finite element analysis and compact thermal models. Parameters of interest include TSV density, heater locations, power density and number of active layers. These thermal simulations yield global temperature distributions, as well as junction temperatures and the locations and magnitudes of hotspots. From the thermal modeling, temperature distributions and their corresponding temperature gradients are used in the mechanical analysis of the structures using finite element analysis for both linear and nonlinear constitutive behavior. The contact method is implemented to account for brittle layers of SiO2 at the CuDB interfaces. Induced stress at the CuDB interfaces and warpage of the full model are analyzed with respect to the coefficient of thermal expansion (CTE) mismatch and applied thermal gradients. In addition, effects of design parameters such as die thickness, TSV pitch, and copper pad size are quantified with respect to the thermal performance and reliability of the package.