Plug-In Hybrid Electric Vehicles (PHEVs) are a promising mid-term solution to reduce the energy demand in the personal transportation sector, due to their ability of storing energy in the battery through direct connection to the electrical grid. However, an important aspect to a successful market acceptability for these vehicles is related to the reliability of the energy storage system. In this scenario, various studies have attempted at investigating the effects of current/power demand, calendar life and operating temperature on battery life, as well as estimating the residual life of the battery under various operating conditions. This paper illustrates the preliminary results of a comprehensive study on Li-ion battery life estimation for PHEVs, predicting their residual life under real-world driving conditions. The methodology adopted is based on both deterministic and stochastic simulations to investigate the effects of electrical and thermal loading on the battery life. To this end, an electro-thermal battery model, inclusive of thermal dynamics and residual life estimation, is developed and utilized in conjunction with a vehicle model, a supervisory controller for PHEV energy management and real-world driving scenarios. Within this framework, the proposed study addresses the impact of the PHEV control parameters on the battery life, namely the vehicle operating modes (charge depleting or charge sustaining), and constraints on the State of Charge (SoC).