During missions on asteroid and lunar and planetary surfaces, space systems and crew health may be degraded by exposure to dust and dirt. Furthermore, for missions outside the Earth‐Moon system, planetary protection must be considered in efforts to minimize forward and backward contamination. This paper presents an end‐to‐end approach to ensure system reliability, crew health, and planetary protection in regolith environments. It also recommends technology investments that would be required to implement this layered engineering defense. Wagner, Sandra Johnson Space Center JSC-CN-30462