Unexpected climatic conditions or extreme climatic events in vineyards are a worldwide problem that requires accurate spatial and temporal monitoring. Satellite-based remote sensing is an important source of data to assess this challenge in a climate-change context. This paper provides a first insight into the capacity of a multiway analysis method applied to Sentinel-2 time series to assess heatwave impacts in vineyards at a regional scale. Multi-way partial least squares (N-PLS) regression was used as a supervised technique to predict the intensity of damage caused to vineyards by the heatwave phenomenon that impacted the vineyards in the south of France in 2019. The model was developed based on available ground truth data of yield losses for 107 vineyard blocks in the Languedoc-Roussillon region and multispectral time-series predictor data for the period May to August 2019. The model showed a performance accuracy (R2) of 0.56 in the calibration set and of 0.66 in the validation set, with a standard error of cross-validation in the calibration set of 12.4% and a standard error of the prediction of yield losses in the validation set of 10.7. The model was applied at a regional scale on 4978 vineyard blocks to predict yield losses using spectral and temporal attributes. The prediction of the yield loss due to heat stress at a regional scale was related to the spatial pattern of maximum temperatures recorded during the extreme weather event. This relation was confirmed by a chi-square test (p < 5%). The introduction of N-PLS insights into the analysis enables the characterisation of heat stress responses in vineyards and the identification of spectro-temporal profiles relevant for understanding the effects of heatwaves on vine blocks at a regional scale.