Nanobiotechnology and nanomedicine are rapidly growing fields, in which nanomaterials (NMs) can lead to enhanced therapeutic efficacy by achieving efficient transport and drug delivery in vivo. The physicochemical properties of NMs have a great impact on their interactions with biological environments and hence determine their biological fates and drug delivery efficiency. Despite rapid advances in understanding the significance of NM properties, such as shape, size, and surface charge, there is a pressing need to engineer and discover how elasticity shapes NM transport. Recently, advances in material synthesis and characterization have promoted investigations into the macroscopic roles and microscopic mechanisms of elasticity to modulate nano-bio interactions. This review will highlight (1) the basic definitions of elasticity and strategies for modulating NM elasticity; (2) advanced techniques for evaluating the effects of elasticity on nano-bio interactions; (3) the macroscopic role of elasticity in the biological fates of NMs, including blood circulation, biodistribution, biological hydrogel penetration, cellular uptake, and intracellular trafficking; and (4) the potential microscopic mechanisms probed by these advanced characterization techniques. Additionally, challenges and future prospects are included. The advanced research discussed in this review will provide guidance to extensively explore the effects and detailed mechanism of elasticity in nano-bio interactions for enhanced drug delivery and developed nanomedicines.