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Entropy generation in nanofluid flows is a complex phenomenon influenced by various factors, including the presence of nanoparticles, temperature gradients, and other effects such as magnetic fields and heat generation. Minimizing entropy generation is crucial for improving the efficiency of nanofluid-based heat transfer systems. In this study, we analyze the irreversibility in cubic autocatalytic Prandtl nanofluid flow by a porous stretchable sheet. To model the nanofluid flow, we consider the effects of Darcy-Forchheimer, thermophoresis, and Brownian motion. Additionally, we account for the impacts of magnetic fields, heat generation, and radiation. Under the implementation of second thermodynamics approach, the entropy generation mechanism is evaluated. Under the certain flow assumptions, the mathematical model is constructed for which numerical treatment is followed via the Runge-Kutta-Fehlberg method (RKF-45) implemented in the Mathematica package. The novel-interpreted outcomes are physically observed in view of flow parameters. Numerical studies are conducted to examine engineering quantities. The results show that fluid velocity decreases with higher magnetic and Forchheimer variables. Temperature increases with greater radiation and heat generation parameters. Concentration and temperature fields are enhanced with higher estimations of the thermophoresis variable. Entropy increases with advanced magnetic variables and the Brinkman number, while the opposite effect is observed for the Bejan number. [ABSTRACT FROM AUTHOR]