The increasing demand for compact, highperformance electronic devices has led to significant challenges in thermal management due to overheating. Traditional cooling methods, such as air convection and passive cooling, often fail to meet the thermal demands of modern electronics. This research proposes an innovative cooling solution using HFO 1234ze nanofluid, a fourth-generation refrigerant with zero ozone depletion potential (ODP) and a low global warming potential (GWP <1), combined with active and passive cooling systems to enhance heat dissipation. The study employs Hotspot Simulator 6.0 to model and simulate the thermal behavior of a compact electronic system, specifically a floor plan equivalent to the Alpha EV6 processor. The simulation results demonstrate that the use of HFO 1234ze nanofluid, with a flow rate of 1100 ml per minute, effectively reduces the temperature of the simulated electronic circuit from 351.80 K to 326.86 K in the Unit Under Test (UUT). This significant temperature reduction highlights the potential of nanofluids in managing heat in high-density electronic systems. The research also integrates thermoelectric cooling (TEC), gravity-assisted heat pipes, and thermal interface materials to further enhance cooling efficiency. The findings suggest that the proposed cooling system not only improves thermal management but also offers an environmentally sustainable solution, positioning HFO 1234ze as a next-generation cooling technology.