The smart diesel program requires the engine electronic control unit to consider additional parameters, such as altitude and climatic conditions, in the mapping calibration process. A specially designed environmental simulation cabin, which can simulate environmental conditions at any longitude and dimension, would allow dynamometer testing to be performed indoors. Considering its high cost, a three-dimensional (3D) computational fluid dynamics (CFD) is needed to guide and/or complement experimental researches. As a result, the main objective of this study was to establish a 3D RANS model (i.e., reasonable computational cost and running time) that can provide in-cylinder details and predict the efficiency of a 6V150 diesel engine under varied operating conditions. A sector mesh approach was employed, considering only the compression, combustion, and expansion periods from intake valve closing to exhaust valve opening. The results indicated that the model simulated cylinder pressure agreed well with the experimental data, with relative errors of less than 6% during the primary compression, combustion, and expansion. Further, the model predicted heat release phasing was inconsistent with the experimental results, with absolute errors of less than one crank angle degree for peak pressure location, CA50, and ignition delay. In addition, the multidimensional model captured the effects of environmental pressure and temperature on spray formation (i.e., the dominant phenomenological event). Moreover, the model reasonably reproduced the effects of engine control variables on performance and emissions. All these observations demonstrated the validity of the selection and calibration of geometry, chemistry, and submodels including turbulence, spray, heat transfer, combustion, etc. Overall, the model was deemed capable of predicting combustion characteristics under extreme conditions, including high-temperature, high-cold, and high-altitude environments, which can facilitate the development of smart engines.