The following paper describes investigations on the impact of harsh environment on shear and tensile strength of multi-material adhesive joints. The samples were made from carbon fiber – epoxy composites, aluminum and two types of advanced steels: abrasion resistant and high-strength. In order to assess the suitability of structural bonding for this sort of applications, it was decided to test two different epoxy-based adhesives, designed for moderate and elevated operating temperatures. The harmful conditions were simulated by means of humidity-temperature cycling tests, according to the SAE standard. The obtained results revealed that even moderately harsh humidity-temperature loads can cause debonding of the joints, even if no external forces are applied. In order to gain insight into this phenomenon, a series of finite element analyses was performed, simulating the exposure of the samples to the chosen environmental conditions. Based on these studies, the temperature expansion coefficient was identified as the crucial factor for the performance of the joints made from dissimilar materials. The results of the described experiments, confirmed by numerical calculations, constitute a guideline for multi-material structural design, supporting this constantly growing branch of modern engineering with a relevant input.