Pistons play a vital role in internal combustion engines, affecting both performance and reliability, and are subjected to intense thermal-mechanical loads that have become more challenging due to improved engine efficiency and power. This study explores the impact of different engine warm-up modes on the combined stress experienced by a piston in a heavy-duty medium-speed diesel engine. This study focused on heavy-duty diesel engines, such as those used in heavy trucks, locomotives, and ships. The authors used a combination of CFD, FEM, and Matlab to consider factors such as oil temperature and flow rate, coolant temperature, component temperature, and boundary conditions during engine transient conditions. The results highlight the significant variations in the thermal and mechanical stress on the piston, particularly in the piston head zone, under different warming-up conditions. It is noted that the variation in oil temperature is a crucial factor affecting the thermal stress on the piston. Low oil temperature can result in reduced heat exchange coefficient and inadequate cooling of the piston due to low flow rate of the cooling oil. During engine warm-up, both thermal and combined stresses reach maximum values and then decrease when the engine reaches stable operating conditions. By selecting appropriate warming-up modes, the quality of the warm-up process and the strength and longevity of the engine could be improved. This study also provides useful insights for technicians to prevent critical conditions that may damage the piston and reduce its strength and lifespan.