The Jet Propulsion Laboratory has a keen interest in exploring icy moons in the solar system, particularly Jupiter’s Europa. Successful exploration of the moon’s surface includes planetary protection initiatives to prevent the introduction of viable organisms from Earth to Europa. To that end, the Europa lander requires a Terminal Sterilization Subsystem (TSS) to rid the lander of viable organisms that would potentially contaminate the moon’s environment. Sandia National Laboratories has been developing a TSS architecture, relying heavily on computational models to support TSS development. Sandia’s TSS design approach involves using energetic material to thermally sterilize lander components at the end of the mission. A hierarchical modeling approach was used for system development and analysis, where simplified systems were constructed to perform empirical tests for evaluating energetic material formulation development and assist in developing computational models with multiple tiers of physics fidelity. Computational models have been developed using multiple Sandia-native computational tools. Three experimental systems and corresponding computational models have been developed: Tube, Sub-Box Small, and Sub-Box Large systems. This paper presents an explanation of the application context of the TSS along with an overview description of a small portion of the TSS development from a modeling and simulation perspective, specifically highlighting verification, validation, and uncertainty quantification (VVUQ) aspects of the modeling and simulation work. Multiple VVUQ approaches were implemented during TSS development, including solution verification, calibration, uncertainty quantification, global sensitivity analysis, and validation. This paper is not intended to express the design results or parameter values used to model the TSS but to communicate the approaches used and how the results of the VVUQ efforts were used and interpreted to assist system development.