The current study scrutinizes the impact of heat and mass transfer on the slip flow of a nanofluid in a rotating system, which is designed by two infinite parallel plates. The effects of a magnetic field, thermal radiation, and chemical reaction are also added to the flow system. Copper oxide (CuO) is considered the nanomaterial with drinking water as the base fluid. The governing partial differential equations are transformed into a system of nonlinear ordinary differential equations with the help of similarity transformations. These equations are solved analytically by employing the least square method (LSM) and the Galerkin method (GM). The results computed by these methods are compared with the numerical method such as the Runge–Kutta method of order four (RK4M). The extensive applications of LSM and GM in comparison with RK4M are also presented. Although the attained outcomes are in good agreement, the results obtained with GM are more accurate than that obtained with LSM. Moreover, the contributions of various fluid parameters on the velocity, temperature, and concentration of the fluid are discussed through graphs. Results reveal that the presence of slip in the boundary declines the fluid velocity. The rotational velocity is enhanced with the increment of the rotation parameter. The magnitude of the skin friction coefficient is reduced by increasing the nanoparticle volume fraction while it grows by rising the magnetic parameter. The Nusselt number shows an enhancement with nanoparticle volume fraction, and it yields a slight reduction by increasing the effect of a magnetic field.