This article focuses on the critical role of advanced computational techniques in enhancing medical diagnostics and treatment planning, especially in procedures like angioplasty. It presents a detailed examination of ballooned catheterization (balloon angioplasty) in a bloodstream carrying tetra-hybrid nanoparticles within a negatively charged stenotic arterial cavity, influenced by a magnetic field. The study models the streaming of blood, considering factors like heat generation, Joule heating, interfacial nanolayers, nanoparticle size, and velocity and thermal slip conditions. The model simplifies complex dynamics through the lubricant and Debye–Hückel linearization approaches and employs the homotopy perturbation method (HPM) for solving dimensionless equations. Mathematica and Matlab are used to illustrate key parameters like velocity, temperature, pressure gradient, wall shear stress (WSS), heat transfer coefficient (HTC), and blood bolus trapping. The study reveals that increasing the balloon catheter’s height boosts blood velocity in the annulus’s central zone, while a thicker interfacial nanolayer diminishes blood temperature and HTC. Larger nanoparticles elevate the blood temperature profile, and increased electro-osmotic parameters enhance the pressure gradient. The tetra-hybrid nano-blood (THNB) shows superior HTC compared to other forms. The study also delves into bolus trapping phenomena, emphasizing the significant changes induced by electro-osmotic forces. Additionally, an artificial neural network (ANN) model, developed using HPM-derived data, accurately predicts WSS and HTC, achieving high accuracy rates of 99.97% in testing and 99.92% in validation for THNB flow. This study paves the way for more targeted, safer, and efficient use of balloon catheters in treating arterial blockages, significantly impacting cardiovascular medicine and patient care.