The incorporation of nanofibrous scaffolds in the hydrogel systems has provided a novel horizon for tissue engineering, drug discovery, and biomedical applications. This chapter digs into the development of hydrogel systems via freeze drying. Freeze-drying technique amalgamates the qualities of the components of a hydrogel into a 3-dimensional, porous structure. Freeze-drying helps in retaining the bioactivity, mechanical properties and precision of controlled porosity, vital for optimum functionality of scaffolds. This chapter also discusses the materials used in the formulation of hydrogel nanofibrous scaffolds and their synergistic performance. It unravels how freezing and sublimation influence the performance and morphology of scaffolds. Furthermore, it confers about the challenges of scalability and reproducibility in their production. Their possible applications in drug delivery systems and tissue engineering have also been acknowledged, with their role in improving therapeutic outcomes.