Numerical simulations of two-dimensional (2D) laminar mixed convection heat transfer and nanofluids flows over forward facing step (FFS) in a vertical channel are numerically carried out. The continuity, momentum, and energy equations were solved by means of a finite volume method (FVM). The wall downstream of the step was maintained at a uniform wall heat flux, while the straight wall that forms the other side of the channel was maintained at constant temperature equivalent to the inlet fluid temperature. The upstream walls for the FFS were considered as adiabatic surfaces. The buoyancy assisting and buoyancy opposing flow conditions are investigated. Four different types of nanoparticles, Al_{2}O_{3}, CuO, SiO_{2}, and ZnO with different volumes' fractions in the range of 1–4% and different nanoparticle diameters in the range of 25–80 nm, are dispersed in the base fluid (water) are used. In this study, several parameters, such as different Reynolds numbers in the range of 100 < Re < 900, and different heat fluxes in the range of 500 ≤ q_{w} ≤ 4500 W/m^{2}, and different step heights in the range of 3 ≤ S ≤ 5.8 mm, are investigated to identify their effects on the heat transfer and fluid flow characteristics. The numerical results indicate that the nanofluid with SiO_{2} has the highest Nusselt number compared with other nanofluids. The recirculation region and the Nusselt number increase as the step height, Reynolds number, and the volume fraction increase, and it decreases as the nanoparticle diameter increases. This study has revealed that the assisting flow has higher Nusselt number than opposing flow.