This work evaluates several compositions of an amorphous solid dispersion (ASD) comprising nimodipine (NMD) as poorly soluble model API in a dual-polymer carrier system. HPMC E5 and Eudragit E were used for the two polymeric carriers. The formulation was designed for hot-melt extrusion (HME) and subsequent strand pelletization. The aim was to identify a formulation window with desired functional ASD performance, i.e. physical stability and immediate API release, as well as processability in strand pelletization. Samples were prepared using small-scale methods, such as vacuum compression molding (VCM) and benchtop extrusion. Miscibility and phase studies were performed for a wide range of polymer ratios and three levels of API content (10–30% w/w). Ternary ASD formulations were phase-separated, yet physically stable upon exposure to elevated temperature/humidity. A study of phase composition showed that the drug molecules were predominantly solubilized in the Eudragit E fraction of the formulation. The miscibility study and Fourier-transform infrared spectroscopy indicated hydrogen (H)bond interactions between NMD and Eudragit E. In HPMC, the amorphous API was dispersed in polymeric matrix and stabilized due to anti-plasticization and the disruption of intermolecular Hbonding between API molecules. Concerning processability in strand pelletization the formulation is limited at high Eudragit E content. NMD and EE-rich phases exhibit low mixture glass transition, low melt stability and brittle breaking behavior upon strand cutting. The high viscosity and yield point of HPMC contributes to the mechanical robustness of the strand at temperatures relevant for processing. Formulation-intrinsic dissolution rates in VCM ASDs developed as an irregular function of polymer ratio, associated with diverse and competitive dissolution mechanisms in the polymers. With regard to the binary system of NMD with HPMC E5, surface crystallization was observed in VCM ASDs. For extruded pellets this was not the case, and a steady trend of formulation-intrinsic dissolution rate across different polymer ratios was observed. These discrepancies indicated a major influence of shear stress during sample preparation on HPMC-based ASD performance. Finally, a feasible formulation window within a polymer ratio of 1:2–2:3 Eudragit E:HPMC was identified in which Eudragit E acts as a dissolution rate enhancer and ASD stabilizer during dissolution.