Cadmium　(Cd)　pollution　has　become　a　global　issue　due　to　industrial　and　agricultural　developments.　However,　the　molecular　mechanism　of　Cd-induced　detrimental　effects　and　relevant　signal　transduction/metabolic　networks　are　largely　unknown　in　marine　fishes.　Here,　greenfin　horse-faced　filefish　(Thamnaconus　septentrionalis)　were　exposed　to　5.0　mg/L　Cd　up　to　7　days.　We　applied　both　biochemical　methods　and　multi-omics　techniques　to　investigate　how　the　gills　respond　to　Cd　exposure.　Our　findings　revealed　that　Cd　exposure　caused　the　formation　of　reactive　oxygen　species　(ROS),　which　in　turn　activated　the　MAPK　and　apoptotic　pathways　to　alleviate　oxidative　stress　and　cell　damage.　Glycolysis,　protein　degradation,　as　well　as　fatty　acid　metabolism　might　assist　to　meet　the　requirements　of　nutrition　and　energy　under　Cd　stress.　We　also　found　that　long-term　(7　days,　“long-term”　means　compared　to　12　and　48　h)　Cd　exposure　caused　the　accumulation　of　succinate,　which　would　in　turn　trigger　an　inflammatory　response　and　start　an　immunological　process.　Moreover,　ferroptosis　might　induce　inflammation.　Overall,　Cd　exposure　caused　oxidative　stress,　energy　metabolism　disturbance,　and　immune　response　in　greenfin　horse-faced　filefish.　Our　conclusions　can　be　used　as　references　for　safety　risk　assessment　of　Cd　to　marine　economic　fishes.　©　2024　by　the　authors.