Buoyancy driven heat transfer of water-based nanofluids in a differentially heated, tilted enclosure is investigated in this study. The governing equations (obtained with the Boussinesq approximation) are solved using the polynomial differential quadrature method for an inclination angle ranging from 0 deg to 90 deg, two different ratios of the nanolayer thickness to the original particle radius (0.02 and 0.1), a solid volume fraction ranging from 0% to 20%, and a Rayleigh number varying from $104$ to $106$. Five types of nanoparticles, Cu, Ag, CuO, $Al2O3$, and $TiO2$ are taken into consideration. The results show that the average heat transfer rate from highest to lowest is for Ag, Cu, CuO, $Al2O3$, and $TiO2$. The results also show that for the particle radius generally used in practice ($\beta =0.1$ or $\beta =0.02$), the average heat transfer rate increases to 44% for $Ra=104$, to 53% for $Ra=105$, and to 54% for $Ra=106$ if the special case of $\theta =90\u2002deg$, which also produces the minimum heat transfer rates, is not taken into consideration. As for $\theta =90\u2002deg$, the heat transfer enhancement reaches 21% for $Ra=104$, 44% for $Ra=105$, and 138% for $Ra=106$. The average heat transfer rate shows an increasing trend with an increasing inclination angle, and a peak value is detected. Beyond the peak point, the foregoing trend reverses and the average heat transfer rate decreases with a further increase in the inclination angle. Maximum heat transfer takes place at $\theta =45\u2002deg$ for $Ra=104$ and at $\theta =30\u2002deg$ for $Ra=105$ and $106$.