<p>Quality by design (QbD) and design of experiments (DoE) have become central to modern pharmaceutical development, yet most guidance and reviews treat formulation development, process optimization, and process validation as largely separate activities. This narrative review focuses specifically on oral tablet products and traces how formulation-level DoE can be used to systematically define, refine, and confirm design space across the full lifecycle of tablet development. Published case studies are organized along a formulation-to-validation pathway, beginning with the translation of the target product profile (TPP) into tablet-specific quality TPPs and critical quality attributes, followed by risk assessment and the selection of appropriate screening, mixture, and response-surface designs for both formulation and process studies. Subsequent sections highlight how DoE outputs support probabilistic and mechanistic design space definition, scale-up and technology transfer, and the alignment of Stage 1–3 process validation activities with QbD principles. Particular attention is given to challenges in integrating DoE with process analytical technology (PAT), model lifecycle management, and data-driven control strategies. This review synthesizes these elements into a practical framework for tablet scientists and manufacturing teams. We outline ways to embed DoE into QbD-based development for tablets and highlight key gaps, including the limited use of probability-based design spaces and digitally enabled validation.</p> Graphical Abstract <p></p>