Understanding the performance of nanofluids in boiling flows is essential to their commercial use in diverse industries. While their impact in single-phase flows is well understood, our knowledge of their thermal behavior in boiling flows remains inconclusive. Furthermore, research on the flow boiling behavior of hybrid nanofluids remains significantly rare compared to that of mono nanofluids. Therefore, this study investigates the effects of tube orientation on the flow boiling behavior of Al2O3-TiO2 water-based hybrid nanofluid and its corresponding mono nanofluids, covering the transition from subcooled to saturated boiling regimes. The results indicate that utilizing a hybrid nanofluid significantly enhances the volume fraction of vapor (VFV) up to 4.43 % and 10.78 % compared to pure water, in vertical and horizontal tubes, respectively. Meanwhile, for Al2O3 and TiO2 mono nanofluids, the VFV experienced an enhancement of up to 3.81 % and 4.28 % in the vertical tube and of up to 8.65 % and 10.41 % in the horizontal tube, respectively. In terms of wall temperature, a slight decrease was observed with nanofluids in vertical tube compared to pure water, whereas an average increase of over 3K was noted in the horizontal tube. Additionally, for the hybrid nanofluid, the heat transfer coefficient (HTC) increased up to 5.59 % in vertical tube but decreased up to 17.69 % in horizontal tube, compared to pure water. Moreover, an enhancement of up to 2.99 % and 3.33 % in vertical tube and a reduction of up to 16.93 % and 17.59 % in horizontal tube was seen in HTC, for Al2O3 and TiO2 mono nanofluids, respectively, compared to pure water.