This article explores the unsteady flow, heat, and mass transport of a Prandtl nanofluid flow over a stretching sheet due to the existence of mixed convection, first-order slip, and chemical reaction. The flow characteristics are analysed for the interaction of thermal and solutal Biot numbers. The system of coupled non-linear leading partial differential equations (PDEs) is converted into non-linear ordinary differential equations (ODEs) with the facilitation of given similarity transformations. Furthermore, these equations are solved by applying a semi-analytical method termed the “Optimal Homotopy Analysis Method” (OHAM) using the computational software MATHEMATICA. The tables and Figures present the numerical computations of the pertinent parameters of the flow problems. The essential findings of this study are for the growing values of the Prandtl parameter, the velocity profile is enhanced, and the temperature profiles show the opposite behaviour. Unsteady parameters reduced the thickness of the heat and moving boundary layers. The temperature profiles are enhanced as the thermal Biot number grows, and similar characteristics can be observed in the solutal Biot number on concentration profiles.