SUMMARYCurrent climate change brings with it a higher frequency of environmental stresses, which occur in combination rather than individually leading to massive crop losses worldwide. In addition to, for example, drought stress (low water availability), also flooding (excessive water) can threaten the plant, causing, among others, an energy crisis due to hypoxia, which is responded to by extensive transcriptional, metabolic and growth‐related adaptations. While signalling during flooding is relatively well understood, at least in model plants, the molecular mechanisms of combinatorial flooding stress responses, for example, flooding simultaneously with salinity, temperature stress and heavy metal stress or sequentially with drought stress, remain elusive. This represents a significant gap in knowledge due to the fact that dually stressed plants often show unique responses at multiple levels not observed under single stress. In this review, we (i) consider possible effects of stress combinations from a theoretical point of view, (ii) summarize the current state of knowledge on signal transduction under single flooding stress, (iii) describe plant adaptation responses to flooding stress combined with four other abiotic stresses and (iv) propose molecular components of combinatorial flooding (hypoxia) stress adaptation based on their reported dual roles in multiple stresses. This way, more future emphasis may be placed on deciphering molecular mechanisms of combinatorial flooding stress adaptation, thereby potentially stimulating development of molecular tools to improve plant resilience towards multi‐stress scenarios.