Tissue engineering is an interdisciplinary field that combines methods, materials, and biological molecules to fabricate newly formed tissues to replace or restore functional organs. Biomaterials-based scaffolds play a vital role in developing new tissue by interacting with human cells. Tissue Engineering scaffolds with ideal characteristics, namely, nontoxicity, biodegradability, and appropriate mechanical and surface properties, are vital for tissue regeneration applications. Although commonly utilized biomaterials can provide physical and chemical properties needed for tissue regeneration, inadequate biomimetic properties, as well as insufficient interactions of cells-scaffolds interaction, still need to be improved for the application of tissue engineering in vivo. Consequently, developing innovative biomaterials-based stimulus-responsive 3D scaffolds that can enhance the mediators of cell adhesion and cellular functioning and that can form functional tissues by providing structural integrity within an appropriate time is much needed. It is possible to achieve some essential features using a single material, so combining two or more materials may fulfill the requirements. In order to achieve a proper scaffold design, a suitable fabrication technique and combination of biomaterials with controlled micro or nanostructures are needed to achieve the proper biological responses. This review highlights the natural polymers, smart materials, and recent advanced techniques currently used to create emerging scaffolds for tissue regeneration applications.