Fire poses a significant risk to Cultural Heritage threatening historical buildings and the artworks they contain. This study seeks to deepen understanding of the physico-chemical processes at play when wall paintings in historic buildings are exposed to fire, with a focus on the impact of combined elevated temperatures and moisture. Specifically, the study aims to quantify the effects on paints, analysing three historically-significant pigments—yellow ochre, red lead, and verdigris—bound in proteinaceous and oil mediums, applied to limestone surfaces. Through systematic examination of the degradation and discoloration induced by heat and moisture, clear trends and insights emerge. Mock-ups of the paints were subjected to a temperature range of 50° to 1100 ℃ simulating open flame conditions. Subsequent experiments replicated the effects of firefighting efforts by introducing saturated moisture conditions. Analysis, using digital photography, colorimetry, UV-VIS spectrophotometry, FTIR-ATR, SEM-BSE and EDX, revealed significant changes in colour, brightness, saturation, and structure, indicative of chemical and physical alteration and degradation phenomena. This study contributes quantitative insights into the effects of temperatures and water on paints used in decorative wall painting, offering valuable guidance for fire prevention and management in Cultural Heritage buildings. These findings inform strategies for preserving cultural artifacts during fire-related disasters, aiding in the implementation of preventive measures and predicting potential damage extent.