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The use of video-imaging data for in-line process monitoring applications has become popular in industry. In this framework, spatio-temporal statistical process monitoring methods are needed to capture the relevant information content and signal possible out-of-control states. Video-imaging data are characterized by a spatio-temporal variability structure that depends on the underlying phenomenon, and typical out-of-control patterns are related to events that are localized both in time and space. In this article, we propose an integrated spatio-temporal decomposition and regression approach for anomaly detection in video-imaging data. Out-of-control events are typically sparse, spatially clustered and temporally consistent. The goal is not only to detect the anomaly as quickly as possible (“when”) but also to locate it in space (“where”). The proposed approach works by decomposing the original spatio-temporal data into random natural events, sparse spatially clustered and temporally consistent anomalous events, and random noise. Recursive estimation procedures for spatio-temporal regression are presented to enable the real-time implementation of the proposed methodology. Finally, a likelihood ratio test procedure is proposed to detect when and where the anomaly happens. The proposed approach was applied to the analysis of high-sped video-imaging data to detect and locate local hot-spots during a metal additive manufacturing process.