Surface-enhanced Raman scattering sensor (SERS) is a promising analytic tool for biomedical diagnoses as it can achieve label-free detection with high sensitivity. SERS sensors are compatible with various biomedical samples, which can be exploited to facilitate next-generation biomedical diagnosis such as point-of-care testing. Recently, intensive efforts for cost-effective and large-area reproducible SERS have been introduced. To address the productivity bottleneck from conventional top-down approaches, laser interference lithography (LIL) was proposed due to its rapid, non-vacuum and large-area capabilities. Herein, we propose multi-angle exposure of LIL as an efficient fabrication method for SERS. Using sequential exposure of laser interference beams with controlled substrate angles, we realize surface patterns with additional structural complexity. In comparison with conventional hole and dot patterns, the complex patterns result in 2-fold enhanced Raman scattered signal of Rhodamine 6G in the given period of 1 u m. We further explore the rationale for pattern periodicity by mathematical modeling and validate the surface enhancement effect by finite-difference time-domain method (FDTD) simulation. In addition, we compare different deposition techniques on the multi-angle LIL patterns, e-beam evaporation and electroplating, and discuss the effect of rough metal aggregation on SERS performances.