Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger that regulates various processes such as biofilm formation and motility. The study investigates how environmental signals, specifically iron, control intracellular c-di-GMP levels in *Pseudomonas aeruginosa*. Iron regulates c-di-GMP levels by modulating the interaction between the iron-sensing protein IsmP and the diguanilate cyclase ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the interaction between IsmP and ImcA, leading to increased c-di-GMP synthesis by ImcA, which promotes biofilm formation and reduces bacterial motility. Structural analysis of the apo-CHASE4 domain and its binding to iron identifies residues defining its specificity. Cryo-electron microscopy of ImcA complexed with a c-di-GMP analog (GMPCPP) reveals a unique conformation where the compound binds to the catalytic pockets and the membrane-proximal side. These findings indicate that the CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes. The study also reports that the ΔismP mutant exhibits reduced biofilm formation and altered colony morphology, suggesting that IsmP is essential for ImcA activity. The crystal structure of CHASE4 and its binding to iron provides insights into how IsmP stimulates ImcA activity. Overall, the results highlight a flexible and specific c-di-GMP signaling process in *P. aeruginosa* that allows the bacteria to adapt to environmental changes.Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger that regulates various processes such as biofilm formation and motility. The study investigates how environmental signals, specifically iron, control intracellular c-di-GMP levels in *Pseudomonas aeruginosa*. Iron regulates c-di-GMP levels by modulating the interaction between the iron-sensing protein IsmP and the diguanilate cyclase ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the interaction between IsmP and ImcA, leading to increased c-di-GMP synthesis by ImcA, which promotes biofilm formation and reduces bacterial motility. Structural analysis of the apo-CHASE4 domain and its binding to iron identifies residues defining its specificity. Cryo-electron microscopy of ImcA complexed with a c-di-GMP analog (GMPCPP) reveals a unique conformation where the compound binds to the catalytic pockets and the membrane-proximal side. These findings indicate that the CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes. The study also reports that the ΔismP mutant exhibits reduced biofilm formation and altered colony morphology, suggesting that IsmP is essential for ImcA activity. The crystal structure of CHASE4 and its binding to iron provides insights into how IsmP stimulates ImcA activity. Overall, the results highlight a flexible and specific c-di-GMP signaling process in *P. aeruginosa* that allows the bacteria to adapt to environmental changes.