Abstract: Gamma-ray imaging is a critical technology in radiation monitoring, nuclear decommissioning, and emergency response at nuclear facilities. However, existing pinhole and Compton imaging methods suffer from limitations such as system complexity and bulky size. Imaging methods based on angular response matrices have garnered attention due to their potential for compact and lightweight structures. However, their imaging performance may depend on detector layout design, and traditional Monte Carlo simulations are too time-consuming to support large-scale layout optimization. To address this issue, a fast response estimation method was proposed based on ray tracing and exponential decay laws, which will simplify the simulation of 633 763 layouts to the simulation of 35 basic scenarios, significantly improving layout screening efficiency. Taking a 3×3×3 cubic grid layout as the subject of study, this method was used to calculate its angular response characteristics. Imaging performance was evaluated across five dimensions: accuracy, angular resolution, directional discrimination, omnidirectional response uniformity, and detection efficiency. The optimized layout selected through this process outperformed random layouts across all metrics, including angular deviation and uniformity, and achieved performance levels comparable to most random layouts while using fewer units. This study provides an efficient computational tool and systematic screening method for the optimized design of omnidirectional γ-imaging detectors based on the Rubik’s cube structure, offering valuable insights for advancing the development of lightweight, omnidirectional radiation imaging technology.