A detailed energetics analysis of the Gulf Stream (GS) and associated eddies is performed using a highresolution multidecadal regional ocean model simulation. The energy equations for the time-mean and timevarying flows are derived as a theoretical framework for the analysis. The eddymean flow energy components and their conversions show complex spatial distributions. In the along-coast region, the cross-stream and cross-bump variations are seen in the eddymean flow energy conversions, whereas in the off-coast region, a mixed positivenegative conversion pattern is observed. The local variations of the eddymean flow interaction are influenced by the varying bottom topography. When considering the domain-averaged energetics, the eddymean flow interaction shows significant along-stream variability. Upstream of Cape Hatteras, the energy is mainly transferred from the mean flow to the eddy field through barotropic and baroclinic instabilities. Upon separating from the coast, the GS becomes highly unstable and both energy conversions intensify. When the GS flows into the off-coast region, an inverse conversion from the eddy field to the mean flow dominates the power transfer. For the entire GS region, the mean current is intrinsically unstable and transfers 28.26 GW of kinetic energy and 26.80 GW of available potential energy to the eddy field. The mesoscale eddy kinetic energy is generated by mixed barotropic and baroclinic instabilities, contributing 28.26 and 9.15 GW, respectively. Beyond directly supplying the barotropic pathway, mean kinetic energy also provides 11.55 GW of power to mean available potential energy and subsequently facilitates the baroclinic instability pathway.