Recent years have witnessed breakthroughs in assistive exoskeletons; both passive and active devices have reduced metabolic costs near preferred walking speed by assisting muscle actions. Metabolic reductions at multiple speeds should thus also be attainable. Musculoskeletal simulation can potentially predict the interaction between assistive moments, muscle-tendon mechanics, and walking energetics. In this study, we simulated devices’ optimal assistive moments based on minimal muscle activations during walking with prescribed kinematics and dynamics. We used a generic musculoskeletal model with tuned muscle-tendon parameters and computed metabolic rates from muscle actions. We then simulated walking across multiple speeds and with two ideal actuation modes–motor-based and spring-based–to assist ankle plantarflexion, knee extension, hip flexion, and hip abduction and compared computed metabolic rates. We found that both actuation modes considerably reduced physiological joint moments but did not always reduce metabolic rates. Compared to unassisted conditions, motor-based ankle plantarflexion and hip flexion assistance reduced metabolic rates, and this effect was more pronounced as walking speed increased. Spring-based hip flexion and abduction assistance increased metabolic rates at some walking speeds despite a moderate decrease in some muscle activations. Both modes of knee extension assistance reduced metabolic rates to a small extent, even though the actuation contributed with practically the entire net knee extension moment during stance. Motor-based hip abduction assistance reduced metabolic rates more than spring-based assistance, though this reduction was relatively small. Our study also suggests that an assistive strategy based on minimal muscle activations might result in a suboptimal reduction of metabolic rates. Future work should experimentally validate the effects of assistive moments and refine modeling assumptions accordingly. Our computational workflow is freely available online.