In recent years, the design of an efficient cooling system together with good thermal efficiency for a new engine is becoming a critical task and therefore the need for an accurate and fast thermo-fluid simulation of engine cooling system is of vital importance. In this study, a detailed CFD and thermal FE simulation of a 12 cylinders V-type medium speed heavy duty diesel engine cooling system has been carried out using ANSYS-CFX commercial code. At first, a global model, for one bank with six cylinders, has been simulated using appropriate mesh density which ensures the accuracy of the results together with reasonable computational time. At this stage, the worst cylinder has been selected based on the wall temperature and the cooling flow rate. Later, using the inlet and outlet boundary conditions extracted from the global model, a series of detailed thermo-fluid analyses have been conducted for the worst cylinder with a finer mesh. The subcooled nucleate boiling heat transfer computation is carried out using the boiling departure lift-off (BDL) model, in which the total heat flux is assumed to be additively composed of a forced convective and a nucleate boiling component. In order to obtain the temperature field for components under consideration, a comprehensive thermal analysis has been preformed coupling with the detailed CFD analyses to reach an accepted value through transferring data between the CFD and FEA software. This method leads to an accurate prediction of the wall temperature and heat flux. It is observed that at hot spots, nucleate boiling occurs for low coolant flow regions specifically around the cylinder head’s exhaust port and liner coolant side wall. Also a considerable increment in the Heat Transfer Coefficient (HTC) has been observed on the superheated regions where the boiling is initiated.