Abstract: Power grid cyber-physical security requires intrusion detection methods that account for the operational consequences of detection errors. However, the existing intrusion detection approaches primarily focus on the predictive performance of learning algorithms, while downstream operational costs are often optimized independently, which can lead to inferior operational performance. To help alleviate this problem, we propose a novel optimization-learning cyber-physical-risk-informed framework that communicates iteratively to minimize power grid operational costs. This framework translates machine learning prediction errors into power grid operational cyber-physical-risk costs. Experimental results on two power grid operation datasets, Industrial Control System (ICS) Cyber Attack and Sherlock, show that the proposed approach improves power grid operation costs compared with the traditional approach.