Power room is the core part of the railway internal combustion locomotives, houses many high-power equipment within a limited space. The ventilation performance of a power room are the key factors that ensure the efficient operation of locomotives. Numerical simulations were conducted to study the indoor and outdoor flow fields of the power room, with focus primarily on the indoor flow field of the locomotive. The effects of locomotive and crosswind speeds on the ventilation performance and indoor flow field of a power room were studied. Furthermore, the effects of fan performance on the power room ventilation were compared and analyzed. The numerical methods used were verified using experimental data. Results showed that as locomotive speed increased, the power room ventilation performance decreased, while the airflow rate of certain power room air intakes increased, with an increase in locomotive speed. Crosswinds significantly increased the power room ventilation quantity, especially when the intakes faced the crosswind. When the crosswind speed surpassed a certain threshold, the intakes on the leeward side of the power room entered an air-leakage state. The indoor flow field distribution of the power room was unaffected by the fan performance. Though the effect of fan performance on the amount of airflow entering the power room varied, the fan performance positively correlated with the overall ventilation performance of the power room. Considering the strong airflow separation caused by the back-step corner of the driver cab, attention should be paid to the placement and intake position of the power room in the design stage.