We propose an efficient method to determine the micro-structural entropic behavior of polymer chains directly from a sufficiently rich non-homogeneous experiment at the continuum scale. The procedure is developed in 2 stages: First, a Macro-Micro-Macro approach; second, a finite element method. Thus, we no longer require the typical stress-strain curves from standard homogeneous tests, but we use instead the applied/reaction forces and the displacement field obtained, for example, from Digital Image Correlation. The approach is based on the P-spline local approximation of the constituents behavior at the micro-scale (a priori unknown). The sought spline vertices determining the polymer behavior are first pushed up from the micro-scale to the integration point of the finite element, and then from the integration point to the element forces. The polymer chain behavior is then obtained immediately by solving a linear system of equations which results from a least squares minimization error, resulting in an inverse problem which crosses material scales. The result is physically interpretable and directly linked to the micro-structure of the material, and the resulting polymer behavior may be employed in any other finite element simulation. We give some demonstrative examples (academic and from actual polymers) in which we demonstrate that we are capable of recovering “unknown” analytical models and spline-based constitutive behavior previously obtained from homogeneous tests.