Meloxicam (MLX) is a non-steroidal anti-inflammatory drug, extensively used for inflammatory diseases and pain treatments, which exhibits five known solids forms. Form IV of MLX, a zwitterionic monohydrate (MH), is an emblematic hydrate case with promissory dissolution properties in a poorly soluble drug. However, the lack of information about MH stability regarding the dehydration process and phase transition impedes the development of further stability studies. A multi-spectroscopic/chemometric approach was implemented coupling middle- (MIR), near-infrared (NIR) and Raman spectroscopies to monitor the heat-mediated dehydration process of MH. The application of multivariate curve resolution-alternating least squares (MCR-ALS) to multi-source spectra by data fusion allow a complete view of the phenomena, improving the selectivity and precision to establish the transition temperatures and to identify involved species. It was revealed a two-step mechanism, where MH changes to Form V at 90 °C obtaining its complete dehydration at 130 °C, Form V remains unchanged during the temperature range 130-190 °C and then the polymorphic conversion to Form I starts, which reaches 100 % at 230 °C before melting MLX (248 °C). The findings of this work allow set targets in the process control of products using MH. Additionally, MCR-ALS detected an event not evidenced by conventional thermal analysis, the transformation of Form V to Form I.