The immune system's complexity and ongoing evolutionary struggle against deleterious pathogens underscore the value of vaccination technologies, which have been bolstering human immunity for over two centuries. Despite noteworthy advancements over these 200 years, three areas remain recalcitrant to improvement owing to the environmental instability of the biomolecules used in vaccines�the challenges of formulating them into controlled release systems, their need for constant refrigeration to avoid loss of efficacy, and the requirement that they be delivered via needle owing to gastrointestinal incompatibility. Nanotechnology, particularly metal−organic frameworks (MOFs) and covalent organic frameworks (COFs), has emerged as a promising avenue for confronting these challenges, presenting a new frontier in vaccine development. Although these materials have been widely explored in the context of drug delivery, imaging, and cancer immunotherapy, their role in immunology and vaccine-related applications is a recent yet rapidly developing field. This review seeks to elucidate the prospective use of MOFs and COFs for biomaterial stabilization, eliminating the necessity for cold chains, enhancing antigen potency as adjuvants, and potentializing needle-free delivery of vaccines. It provides an expansive and critical viewpoint on this rapidly evolving field of research and emphasizes the vital contribution of chemists in driving further advancements. CONTENTS 1. Introduction to Vaccines and Immuno-Therapeutics and Current Limitations in the Landscape of Vaccine Technology 3013 2. Unique Structural Features of MOFs/COFs 3015 3. Advantages of Using MOFs/COFs To Fill the Gap in Current Vaccine Technology 3017 3.1. Thermodynamic Stability of MOFs 3017 3.2. Kinetic Lability 3019 3.3. Functional Modification 3019 3.4. Needle-Free Delivery 3019 4.