The current examination explores the magnetohydrodynamic flow and transport behavior of a Casson-based blood-derived hexa-hybrid nanofluid via a vertically oriented, mildly stenotic artery using a fractional-order framework. The hexa-hybrid nanofluid is formulated by dispersing Au, Cu, ZnO, Ag, MgO and TiO2 nanoparticles into blood, and the flow is considered highly pulsatile. Mathematical modelling is developed from the conservation laws of mass, momentum, and energy, followed by nondimensionalization under the mild-stenosis approximation. To extend the classical model to its fractional form, the Caputo–Fabrizio fractional derivative is incorporated, enabling closed-form analytical expressions for velocity and temperature through combined Laplace and Hankel transforms. The graphical results highlight the influence of key physical factors on velocity, temperature, and entropy production. The inclusion of hexa-hybrid nanoparticles notably enhances the thermal characteristics of blood due to the substantial rise in effective thermal conductivity. The velocity increases with higher Casson parameter values, whereas temperature decreases as the fractional-order parameter intensifies. Furthermore, entropy generation is found to rise with increasing thermodynamic parameters, while the Bejan number correspondingly decreases, reflecting dominant irreversibility effects within the system.