The heat transfer and the hydraulic performance of laminar flow using water–CuO nanofluid and pure water in smooth and complex channels with embedded hollow half‐spheres are numerically studied over a range of Reynolds numbers. Pure water is first used as the coolant for all selected configurations, followed by low‐volume fractions (3% and 5%) of water–CuO nanofluid in the optimal configuration. Three configurations are evaluated by varying the number and diameter of the opposing half‐spheres. The results show that the heat transfer coefficient for microchannels with half‐spheres increases, reaching up to 3.5 times that of smooth microchannels. Additionally, within the same Reynolds number range, the friction factor increases by up to 50%. The use of nanofluids results in a 6% and 14% increase in the heat transfer coefficient for concentrations of 3% and 5%, respectively, compared with pure water. These enhancements are directly correlated with the increase in thermal conductivity of the nanofluids relative to water.