Li-ion secondary rechargeable batteries are becoming the preferred solution to store energy on board of new generation electric and hybrid vehicles or manage renewable energy in stationary applications. However, Li-ion batteries (LIBs) are still suffering limited lifetime, high cost and significant safety issues increasing their time to mass market. Thermal runaway is still nowadays considered as a major hazard of LIBs. This multiscale and multistep phenomenon originating at the microscale level potentially leads to uncontrolled fire and explosion of the battery. This work is focused on the development and validation of a 3D physical model of the LIB electro-thermal behavior nearby thermal runaway conditions. A combined modeling and experimental investigation provides a better understanding of the mechanisms leading to thermal runaway of LIBs, and of the ageing influence on this process. One major outcome of this work is also the proven fact that calendar ageing leads to a delayed onset of the cell self-heating temperature with a thermal runaway starting at a lower temperature. This is supported by computer simulations showing that the thickening of the solid electrolyte interface (SEI) hinders the diffusion of Li ions, which delays the degradation of the negative electrode and the occurrence of thermal runaway.