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Summary A dynamic assembly of nuclear and cytoplasmic processes regulate gene activity. Hypoxic stress and the associated energy crisis activate a plurality of regulatory mechanisms including modulation of chromatin structure, transcriptional activation and post‐transcriptional processes. Temporal control of genes is associated with specific chromatin modifications and transcription factors. Genome‐scale technologies that resolve transcript subpopulations in the nucleus and cytoplasm indicate post‐transcriptional processes enable cells to conserve energy, prepare for prolonged stress and accelerate recovery. Moreover, the harboring of gene transcripts associated with growth in the nucleus and macromolecular RNA–protein complexes contributes to the preferential translation of stress‐responsive gene transcripts during hypoxia. We discuss evidence of evolutionary variation in integration of nuclear and cytoplasmic processes that may contribute to variations in flooding resilience.