Oxygen (O2) is an inhibiting factor for plant growth and development in submerged and flooding environments. Plants experience different O2 concentrations, such as normoxia, hypoxia, and anoxia, which can change over space and time. Plants have evolved various morphological, physiological, and biochemical adaptations to withstand low O2 stress, many of which have been well investigated. This review provides a detailed analysis of how plants respond to hypoxia, a significant stress factor primarily caused by flooding. Hypoxia affects plants at various cellular, developmental, and environmental levels. This review highlights genetic, molecular, and metabolic adaptations crops employ to cope with O2 deficiency. The roles of various transcription factors (TFs) and gene regulation mechanisms in enabling plants to modulate their physiological responses under hypoxic conditions are notable. The review also identifies a significant gap in research on plant responses during reoxygenation, the phase of returning to normal O2 levels, especially under natural lighting conditions. This transition poses ROS generation and photoinhibition challenges, affecting plant recovery post-hypoxia. We discuss various strategies to enhance plant hypoxia tolerance, including traditional breeding, genetic modification, and grafting techniques. It emphasizes integrating these approaches with a comprehensive understanding of hypoxia sensing and response mechanisms. We underscore the complexity of plant adaptations to hypoxia and the need for continued research in this field, especially in the face of global climate change. This is vital for developing sustainable agricultural practices and ensuring future food security.