This trial aimed to integrate metadata that spread over farm-to-fork continuum of 110 Protected Designation of Origin (PDO)Maine-Anjou cows and combine two statistical approaches that are chemometrics and supervised learning; to identify the potential predictors of beef tenderness analyzed using the instrumental Warner-Bratzler Shear force (WBSF). Accordingly, 60 variables including WBSF and belonging to 4 levels of the continuum that are farm-slaughterhouse-muscle-meat were analyzed by Partial Least Squares (PLS) and three decision tree methods (C&RT: classification and regression tree; QUEST: quick, unbiased, efficient regression tree and CHAID: Chi-squared Automatic Interaction Detection) to select the driving factors of beef tenderness and propose predictive decision tools. The former method retained 24 variables from 59 to explain 75% of WBSF. Among the 24 variables, six were from farm level, four from slaughterhouse level, 11 were from muscle level which are mostly protein biomarkers, and three were from meat level. The decision trees applied on the variables retained by the PLS model, allowed identifying three WBSF classes (Tender (WBSF ≤ 40 N/cm2), Medium (40 N/cm2 < WBSF < 45 N/cm2), and Tough (WBSF ≥ 45 N/cm2)) using CHAID as the best decision tree method. The resultant model yielded an overall predictive accuracy of 69.4% by five splitting variables (total collagen, µ-calpain, fiber area, age of weaning and ultimate pH). Therefore, two decision model rules allow achieving tender meat on PDO Maine-Anjou cows: (i) IF (total collagen < 3.6 μg OH-proline/mg) AND (µ-calpain ≥ 169 arbitrary units (AU)) AND (ultimate pH < 5.55) THEN meat was very tender (mean WBSF values = 36.2 N/cm2, n = 12); or (ii) IF (total collagen < 3.6 μg OH-proline/mg) AND (µ-calpain < 169 AU) AND (age of weaning < 7.75 months) AND (fiber area < 3100 µm2) THEN meat was tender (mean WBSF values = 39.4 N/cm2, n = 30).