Performance of all-solid-state batteries (ASSBs) with polycrystalline LiNixCoyMnzO2 (NMC) cathodes is limited by particle cracking and cathode–solid-electrolyte (SE) debonding driven by anisotropic lithiation and stress localization, the coupled diffusion-mechanics mechanisms remain poorly understood. In this work, we develop a fully coupled anisotropic chemo-mechanical phase-field framework that extends prior one-way and partially coupled models to predict lithiation heterogeneity and stress localization in polycrystalline NMC cathodes embedded in an SE matrix. Finite-element simulations on Voronoi microstructures parameterize chemical and mechanical anisotropy through αD (diffusivity) and αΩ (eigenstrain), and quantify intra- and intergranular tensile stresses together with spatial lithium and stress fields. We confirm that coupled anisotropy drives nonuniform lithiation and tensile hot spots with a non-monotonic stress response. Moreover, the eigenstrain anisotropy dominates stress amplification, while diffusion anisotropy primarily governs lithium intermittency. Furthermore, mechanical stability requires integrated optimization across particle-level and grain-level, rather than independent parameter tuning. Composite-SE simulations show a stiffness tradeoff: stiffer SEs increase interfacial stress and delamination propensity, whereas compliant SEs promote intraparticle stress localization and fracture. Applied stack pressure primarily mitigates early-stage stresses. These results provide mechanistic insight into microstructuremediated degradation in ASSBs and offer design guidelines for high-performance solid-state cathodes.