Numerical analysis is performed to deduce the effect of aspect ratio (AR) and inclination of a rough-walled cavity on heat transfer, fluid flow, and entropy generation due to natural convection for Rayleigh number (Ra = 105). The cavity is filled with Al2O3-water nanofluid of 0.05 solid volume fraction. The natural convection process is caused by the temperature difference between the left hot wall and the right cold wall of the cavity. The walls are subjected to slip boundary conditions and the slip velocity is characterized by the Knudsen number (Kn = 0.5). The profile of the rough surface is generated by Weierstrass-Mandelbrot (W-M) function. Numerical simulations have been performed using Finite Element based software COMSOL Multiphysics 6.0. The AR is varied in the range of 0.5 to 4, and the inclination of the cavity is kept at 0°, 30°, and 60°. The numerical results are exhibited in terms of isotherms, streamlines, entropy generation due to heat transfer, and fluid friction irreversibilities. It is observed that the slip velocity on the walls has a strong influence on the fluid flow. Entropy generation due to fluid friction is found to increase with the rise in AR up to 2 and then it starts declining. The entropy generation due to fluid friction irreversibility at the center of the cavity is minimal, so the Bejan number is close to unity. Cavity with an inclination of 30° gives the maximum Nusselt number at any value of AR. Notably, the total entropy generation is observed to reach its maximum at α = 60° and minimum at α = 30°, offering comprehensive insights into the interplay of geometric and flow parameters within the cavity.