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Exosuits are emerging as promising in assisting with activities of daily living. In the design phase of an exosuit, it is fundamental to maximize its portability. The goal of this work was to identify the best cable routing configuration for an upper limb cable-driven exosuit to assist elbow flexion. Simulations were run in OpenSim. Different cable configurations were evaluated. The goal was to minimize the overall tension of the cables to reduce the device's power consumption and torque requirements. The optimal configuration was evaluated in simulation for different percentages of assistance to study its effects in terms of muscle activation and joint reaction forces. We then tested three different configurations on a test bench to both evaluate the motor current and their effect on the pronation/supination of the elbow. Simulation results suggested that a double cable configuration might help to lower the motor torque and power consumption. This conclusion was supported by the experimental results, in which the motor current was reduced by 12.5% with respect to the single cable configuration. Simulation results also showed that the optimal configuration lowered muscle activation without greatly affecting joint reactions at the elbow, even though it might cause unwanted pronation/supination, as experimental results confirmed. However, since a double configuration results in greater complexity and reduced efficiency, single-cable solutions still represent a good option.