Due to the high acid, oxygen and water contents of fast pyrolysis oil, it requires the improvement of its fuel properties by further upgrading, such as catalytic hydrodeoxygenation (HDO). In this study, Nb2O5 was evaluated as a support of Pd-based catalysts for HDO of fast pyrolysis oil. A Pd/SiO2 catalyst was used as a reference. Additionally, the impact of iron as a promoter in two different loadings was investigated. The activity of the synthesized catalysts was evaluated in terms of H2 uptake and composition of the upgraded products (gas phase, upgraded oil and aqueous phase) through elemental analysis, Karl Fischer titration, GC-MS/FID and 1H-NMR. In comparison to SiO2, due to its acid sites, Nb2O5 enhanced the catalyst activity towards hydrogenolysis and hydrogenation, confirmed by the increased water formation during HDO and a higher content of hydrogen and aliphatic protons in the upgraded oil. Consequently, the upgraded oil with Nb2O5 had a lower average molecular weight and was therefore less viscous than the oil obtained with SiO2. When applied as a promoter, Fe enhanced hydrogenation and hydrogenolysis, although it slightly decreased the acidity of the support, owing to its oxophilic nature, leading to the highest deoxygenation degree (42.5 wt.%) and the highest product HHV (28.2 MJ/kg).