The neural efficiency hypothesis postulates an inverse relationship between intelligence and brain activation. Previous studies suggest that sex and task modality represent two important moderators of the neural efficiency phenomenon. In males, the relationship between intelligence and activation was primarily found in frontal areas during visuo-spatial tasks, while in females neural efficiency could be observed in left centroparietal and temporal regions during verbal tasks (Neubauer et al., 2005). Since most of the existing studies on neural efficiency have used ERD in the EEG as a measure of brain activation, the central aim of this study was to gain more insight into the exact localization of this phenomenon. Using fMRI, 20 males and 20 females were confronted with a verbal and a visuo-spatial Posner task, employing an event-related approach. During the visuo-spatial task, positive relationships between visuo-spatial intelligence and activation were found for females in task-relevant as well as task-irrelevant tasks, and for males in areas associated with the right insula and the posterior cingulum. During the verbal task, verbal intelligence was negatively correlated with activation in occipital areas throughout the whole sample. Additionally, less intelligent individuals showed a stronger deactivation in parts of the brain-default network. This was found during the visuo-spatial task for females and males, during the verbal task only for females. Further results suggest that more visuo-spatially intelligent people compensate for an increase in task difficulty with stronger activation in task-relevant areas, while there is no relationship between task difficulty and activation in less intelligent individuals. The findings of this study provide a deeper insight into the neural efficiency phenomenon, but also outline possible challenges in the investigation of neural efficiency with fMRI.