The front rail, as one main energy absorption component of vehicle front structures, should present steady progressive collapse along its axis and avoid bending collapse during the front oblique impact, but when the angle of loading direction is larger than some critical angle, it will appear bending collapse causing reduced capability of crash energy absorption. This paper is concerned with crashworthiness design of the front rail on a vehicle chassis frame structure considering uncertain crash directions. The objective is to improve the crash direction adaptability of the front rail, without deteriorating the vehicle's crashworthiness performance. Magic Cube (MQ) approach, a systematic design approach, is conducted to analyze the design problem. By applying Space Decomposition of MQ, an equivalent model of the vehicle chassis frame is generated, which simplifies the design problem. Based on this model, a two-layered front rail is proposed using a multi-step multi-domain topology optimization method and a response surface method. Numerical simulations are carried out with Altair/Hypermesh and LS-DYNA to compare the crashworthiness performances of the original front rail and the proposed two-layered design. The result shows that the two-layered front rail, with a reduced weight by 17%, can absorb 46% more energy in the 30 degree front impact than the original design, meanwhile, the proposed design eliminates the bending collapse on its rear end when the angle of loading direction reaches the critical angle. The energy absorption capability and the direction uncertainty adaptability of the front rail are significantly improved.