The growing demand for energy-efficient automotive air-conditioning (AAC) systems has highlighted the need for advanced lubrication methods to improve performance and reduce fuel consumption. Despite many advancements, more lubrication system technologies (e.g. nano-lubricants) need to be developed to achieve effective thermal and tribological performance, especially in actual automobile systems. Thus, the need for this research is to analyse various nano-lubricant formulations and evaluate its thermal and tribological performance in real-world working conditions. The effect of different compositions of the nano-lubricant on the cooling capacity, compressor power consumed, and the coefficient of performance of the system is tested in a test rig. Predictive modelling of the system is designed using a deep echo state network (ESN), and the optimization of the nano-lubricant formulation is performed using an artificial satellite search algorithm, which uses data generated during tests to optimize the formulation for maximum overall efficiency. The results show that the hybrid nano-lubricant (CuO–TiO2/PVE composite) improves system characteristics, such as a 40.23% reduction in the friction coefficient and 23% reduction in wear scar diameter. Besides other factors, the compressor efficiencies are increased by 15–20%, the power consumptions are decreased by 8–10% and the cooling loads are increased by 12% while 1% of nanoparticles are used with PVE. These features are important factors for automotive applications and present an opportunity for the automotive industry. The results suggest that nanoparticles could be an effective means to improve the life and efficiency of AAC systems and hence could be used in the refrigeration system of a vehicle to improve the performance.