The thermoelectric properties of defected graphene nanoribbons (GNRs) and multi-junction (MJ) GNRs coupling periodic armchair sections of different width are analyzed by means of Green’s function techniques to simulate electron and phonon transport. Among the different strategies likely to enhance the thermoelectric performance, the effects of edge disorder and random vacancies are shown to be small since they lead to the concomitant degradation of the phonon thermal conductance and of the electronic conductance, which finally reduces the thermoelectric factor ZT. However, the periodic distribution of vacancies and the structuring of GNRs in MJ-GNRs both lead to the enhancement of the figure of merit ZT. In the latter case, in addition to the strong reduction of the phonon thermal conductance, an effect of resonant tunneling of electrons allows retaining high electronic conductance and enhancing significantly the thermopower. Finally, by introducing a periodic distribution of vacancies in the MJ-GNR, the maximum value ZT=0.4 is reached at room temperature.