Wood as an ecofriendly and renewable natural material has been extensively modified through various delignification protocols to preserve its natural structure and fiber direction. The increased porosity and permeability of wood scaffold thus provide excellent opportunities for material infiltration and densification. Wood features in hierarchical structure and biocompatibility are combined with cutting-edge processings to overcome the weaknesses for vast applications. These new modifications have explored the great potentials of wood as a next-generation structural and functional material. This review updates the state-of-the-art physicochemical modifications and strategies to prepare versatile wood hydrogels, aerogels, membranes, and fibers with different physicochemical features. Discussion is elaborated to explore the immense breadth of wood as next-generation material for applications in biomedical, energy storage, sensors, separation, and buildings. Finally, the main challenges of wood scaffold engineering are represented along with potential solutions and directions for developing wood-based high-performance structural and functional materials.