Lipid nanoparticles (LNPs) have emerged as a promising delivery system for messenger RNA (mRNA) therapeutics, particularly in the development of mRNA vaccines against diseases such as COVID-19. LNPs protect mRNA from degradation, facilitate cellular uptake, and enable the release of mRNA within cells. They have been successfully used in clinical settings, with two authorized COVID-19 vaccines, mRNA-1273 and BNT162b2, utilizing LNPs to deliver antigen mRNA. This review discusses the design of LNPs for mRNA delivery, the physiological barriers they must overcome, and the key considerations for clinical translation, including good manufacturing practices, stability, storage, and safety. It also highlights preclinical and clinical studies of LNP-mRNA formulations for infectious diseases, cancer, and genetic disorders. The review outlines the development of various lipid materials for mRNA delivery, including cationic lipids, ionizable lipids, and other lipid components, and discusses their roles in enhancing mRNA delivery efficiency and therapeutic outcomes. The review also addresses the challenges and future possibilities for LNP-mRNA technology, including the need for targeted delivery, improved stability, and reduced immunogenicity. The review emphasizes the importance of optimizing lipid nanoparticle formulations to achieve effective and safe mRNA delivery for a wide range of therapeutic applications.Lipid nanoparticles (LNPs) have emerged as a promising delivery system for messenger RNA (mRNA) therapeutics, particularly in the development of mRNA vaccines against diseases such as COVID-19. LNPs protect mRNA from degradation, facilitate cellular uptake, and enable the release of mRNA within cells. They have been successfully used in clinical settings, with two authorized COVID-19 vaccines, mRNA-1273 and BNT162b2, utilizing LNPs to deliver antigen mRNA. This review discusses the design of LNPs for mRNA delivery, the physiological barriers they must overcome, and the key considerations for clinical translation, including good manufacturing practices, stability, storage, and safety. It also highlights preclinical and clinical studies of LNP-mRNA formulations for infectious diseases, cancer, and genetic disorders. The review outlines the development of various lipid materials for mRNA delivery, including cationic lipids, ionizable lipids, and other lipid components, and discusses their roles in enhancing mRNA delivery efficiency and therapeutic outcomes. The review also addresses the challenges and future possibilities for LNP-mRNA technology, including the need for targeted delivery, improved stability, and reduced immunogenicity. The review emphasizes the importance of optimizing lipid nanoparticle formulations to achieve effective and safe mRNA delivery for a wide range of therapeutic applications.