This study applies constructal theory to conduct a numerical optimization of three-dimensional cylindrical microcooling channels with the solid structure subjected to internal heat generation. The cylindrical channels are designed as variable cross-section configurations that experience conjugate heat transfer and fluid flow, where water is used as the coolant. The research aims to optimize the channel configurations subject to a fixed global solid material volume constraint. The key objectives are to minimize the global thermal resistance and friction factor. The coolant is pushed through the channels by pressure drop represented as Bejan number. The main design parameters are the inlet and outlet diameters at a given porosity. The channel configuration and the structure elemental volume are permitted to change to find the best design parameters that minimized thermal resistance and friction factor, so that the cooling effect is enhanced. An ANSYS FLUENT code is used to obtain the best optimal parameter of the configuration that enhances thermal performance. The influence of Bejan number on optimized inlet and outlet diameters led to How to cite this article: Olakoyejo OT, Adelaja AO, Adewumi OO, Oluwo AA, Bello SK, Adio SA. Constructal heat transfer and fluid flow enhancement optimization for cylindrical microcooling channels with variable cross-section.