As a common complaint in contemporary society, mental fatigue is a key element in the deterioration of the daily activities known as time-on-task (TOT) effect, making the prediction of fatigue-related performance decline exceedingly important. However, conventional group-level brain-behavioral correlation analysis has the limitation of generalizability to unseen individuals and fatigue prediction at individual-level is challenging due to the significant differences between individuals both in task performance efficiency and brain activities. Here, we introduced a cross-validated data-driven analysis framework to explore, for the first time, the feasibility of utilizing pre-task idiosyncratic resting-state functional connectivity (FC) on the prediction of fatigue-related task performance degradation at individual level. Specifically, two behavioral metrics, namely ∆RT (between the most vigilant and fatigued states) and TOTslope over the course of the 15-min sustained attention task, were estimated among three sessions from 37 healthy subjects to represent fatigue-related individual behavioral impairment. Then, a connectome-based prediction model was employed on pre-task resting-state FC features, identifying the network-related differences that contributed to the prediction of performance deterioration. As expected, prominent populational TOT-related performance declines were revealed across three sessions accompanied with substantial inter-individual differences. More importantly, we achieved significantly high accuracies for individualized prediction of both TOT-related behavioral impairment metrics using pre-task neuroimaging features. Despite the distinct patterns between both behavioral metrics, the identified top FC features contributing to the individualized predictions were mainly resided within/between frontal, temporal and parietal areas. Overall, our results of individualized prediction framework extended conventional correlation/classification analysis and may represent a promising avenue for the development of applicable techniques that allow precaution of the TOT-related performance declines in real-world scenarios.