This study investigates 2-D natural convection heat transfer within an irregular wall cavity filled with nanofluid, employing a computational approach. The rough profile of the cavity surface is generated using the Weierstrass-Mandelbrot (W-M) function, and various parameters such as Rayleigh number ( 10 3 ≤ Ra ≤ 10 6 ), Knudsen number ( 0 ≤ Kn ≤ 1.5 ), solid volume fraction ( 0 ≤ ϕ ≤ 0.15 ), and amplitude of the irregular rough wall ( 0 ≤ A 1 ≤ 0.1 ) are varied. The nanofluid consists of water as the base fluid and aluminum oxide (Al2O3) nanoparticles. Heat transfer characteristics are analyzed using the Nusselt number (Nu), while entropy generation is quantified to optimize thermal system efficiency. Grid sensitivity analysis and validation against existing literature are conducted to ensure the accuracy of the numerical methodology. Notably, the study demonstrates that increasing the slip velocity at the cavity wall enhances convection within the cavity, leading to a substantial increase in Nu. At Ra = 106, the Nu increases by 53.52% when Kn changes from 0 to 1. Furthermore, the study highlights the significant influence of nanoparticle volume fraction on Nu, showing that as the volume fraction increases, Nu also increases, indicating improved convective heat transfer performance. The Nu for a cavity with an amplitude of 0.1 is roughly 2.5 times higher compared to a smooth-walled cavity at Ra = 106. Increased surface irregularity enhanced turbulence intensity and mixing, leading to stronger convective currents. The novelty of this study lies in examining natural convection in irregular shaped cavities with wall-slip conditions, which are common in practical applications such as solar collectors, microelectronic devices, energy storage units, industrial furnaces, etc. This study offers valuable insights into the thermal behavior of rough enclosures filled with nanofluids, which will facilitate the optimization of heat transfer systems to minimize energy losses.