This paper explores the interplay between structural and dynamic complexity factors, uncovering the mechanisms that underpin it. Four in-depth inductive case studies, which comprised semi-structured interviews with senior operations and SC managers as well as the use of companies' official documents and other secondary data, were carried out. The study offers a deep understanding and provides rich empirical descriptions of the interplay between structural and dynamic complexity factors. A general framework to represent different aspects of this interplay is also introduced, i.e. the House of Supply Chain Complexity diagram; as a practical tool for mapping the complexity factors and inferring the prevailing interplay mechanisms in specific cases. The results show four interplay mechanisms between structural and dynamic complexity factors: silo-thinking, localism, limited adaptability and increased uncertainty. Testable propositions are presented with relevant insights on the interplay between a wide range of structural and dynamic complexity factors. Research implications relate to: (i) a general framework usable to further investigate interplay mechanisms at factors level and in different SC contexts and (ii) theory building on the suggested interplay mechanisms. We contribute to enhance contingency research claiming for the importance of considering the cumulative effect of contingency factors on SC performance. The results also suggest that managers can accommodate the mechanisms of silo-thinking and increased uncertainty by information sharing and organizational means, but the interplay mechanisms of localism and limited adaptability appear to be more related to the physical structure of SC elements and thus mainly manageable by reducing complexity, i.e. reducing the factors involved in the interplay.