Twin-screw melt granulation (TSMG) is a promising continuous process for producing solid pharmaceutical dosage forms. However, the application of Near-Infrared (NIR) spectroscopy as a Process Analytical Technology (PAT) tool in this context is still underexplored. This study evaluates the feasibility of using in-line NIR spectroscopy combined with chemometric modeling to monitor key formulation and process variables in TSMG, including binder content, screw configuration, and sample temperature. Experiments used lactose monohydrate and polyethylene glycol (PEG) 6000 as a model formulation. Blends were processed under four conditions, varying PEG content (10–20 wt%), screw design (kneading or conveying), and screw speed (100–175 rpm). Granules were analyzed in-line using NIR spectroscopy (1100–2300 nm), collecting 23 spectra per condition. Spectral data were preprocessed (SNV, derivatives) and analyzed via Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression. These conditions reflected a design space supported by prior studies¹. Additionally, ungranulated mixtures with 15 wt% PEG were conveyed through the granulator and their spectra were compared to granulated samples. Measurements were taken immediately after production and after cooling to ambient temperature to assess sample temperature effects. PLS models showed excellent predictive performance for PEG content, with R² values of 0.9998 (raw) and 0.9983 (SNV). PCA graphically discriminated between granulated and non-granulated samples, and between screw configurations, especially using raw and SNV data. Temperature effects on spectral profiles were evident: granules measured post-processing and at room temperature formed separated PCA clusters, especially with derivative preprocessing. These findings confirm that NIR spectroscopy, combined with multivariate data analysis, enables non-destructive, real-time monitoring of formulation and process parameters in TSMG, supporting its integration as a robust PAT tool for enhancing control and product quality in pharmaceutical continuous manufacturing.