The objective of this investigation is to explore the various factors affecting the heat exchange characteristics of a heating block that is cooled using hybrid nanofluids. The results from this investigation can be useful to enhance the thermal performance and heat transmission efficiency in the design of thermal engineering equipment. To achieve this, we conducted a (3-D) numerical investigation of mixed convection within an L-cavity filled with hybrid nanofluid. Within this cavity, a heating block is located either on the west wall (Case VB) or on the bottom wall (Case HB). In both cases, cold hybrid nanofluids were introduced at a constant temperature and flowed through a portion of the top wall, while the remaining walls were considered adiabatic. The finite volume method along with the Boussinesq approximation were used to solve the governing equations. The numerical results were presented in the form of iso-lines, global Nusselt numbers, and isotherms for several thermal parameters, including Reynolds numbers, Richardson numbers, and hybrid volume fraction. Our results indicated that for all Richardson numbers and in both configurations, VB and HB, the total Nusselt number increased with increasing Reynolds numbers and volume fraction of particles, except in the case of configuration HB when the volume fraction (ϕ = 0%) and the Re ≥ 840, and that when the heated block was repositioned from configuration, HB, to configuration, VB, heat transfer increased significantly by 51.16%. Furthermore, we uncovered intriguing results when comparing the two configurations, VB and HB.