Sending humans to the Moon and Mars in the near future requires appropriate infrastructure to support and subsequently sustain human activities. This includes infrastructure to shield from environmental conditions, generate energy, and facilitate mobility and communication. Construction of such infrastructure aims to use in-situ resources and reduce the use of supplies from Earth. The establishment and maintenance of the required infrastructure, equipment, and hardware involves the development of adequate manufacturing techniques, which can enable maximal use of the local resources. Those techniques can be based on processing of local materials into construction materials, extraction of useful elements from local materials or in combination with materials brought from Earth. The required manufacturing techniques address the range of needs for sustained human activities, from smaller scale manufactured items to large built structures. The design of such structures is associated with a number of space systems’ engineering challenges, ranging from the accurate definition of all resource budgets (mass, volume, power, data) to the design of the interfaces between all subsystems making use of these resources. The interplanetary spacecraft used to transport the required materials (and eventually, crew) from Earth to the final site would probably need to be designed ad-hoc for this specific application, given its peculiar mass and volume constraints, especially in case a reusable concept is adopted. Other engineering aspects involved in the design of the infrastructure systems include the selection of an appropriate power generation approach and the definition of the radiation environment in order to provide sufficient shielding to the habitats. This Spool CpA #4 issue investigates challenges of designing, engineering, constructing, operating, and maintaining off-Earth infrastructure.