Lipid nanoparticles (LNPs) are the most commonly used delivery vectors for messenger RNA (mRNA) in clinical applications. They protect mRNA from degradation, enhance cellular uptake, and facilitate cytoplasmic release. LNPs have high drug-loading capacity, high encapsulation efficiency, sustained release, high stability, low toxicity, and enhanced efficacy. Three nucleic acid medicines based on LNPs have been approved, including Patisiran, BNT162b2, and mRNA-1273. These applications demonstrate the success of LNP delivery systems for gene drugs and vaccines. The momentum of preclinical research and clinical trials for mRNA–LNP drugs is increasing. However, the current focus is predominantly on liver delivery, leading to a prevalence of liver-targeted delivery among LNPs. DLin-MC3-DMA (MC3) LNPs are the most representative vector for liver-targeted delivery. Both SM-102 and ALC-0315 are MC3 LNPs that primarily deliver mRNA to the liver after intravenous injection. However, LNPs for extrahepatic-targeted mRNA delivery are still in the early stages of development. To fully utilize the advantages of mRNA technology, such as its low cost, high efficiency, and short developmental cycles, the development of an extrahepatic-targeted delivery strategy for mRNA–LNPs is of great significance. Current research is focused on enhancing the accuracy of mRNA–LNP delivery to specific cells, tissues, or organs to improve the therapeutic effect and minimize potential side-effects. In this review, we summarize the latest strategies for the targeted delivery of mRNA–LNPs to cells and tissues, including tissue-specific or cell-specific LNPs, following different injection modes. The review also highlights the preclinical and clinical research progress of mRNA–LNPs in the treatment of cancer, infectious diseases, and hereditary diseases. Finally, the current challenges and potential future research directions are briefly reviewed. LNPs are composed of ionizable cationic lipids (ICLs), helper lipids, cholesterol, and polyethylene glycol (PEG) lipids. ICLs are key factors that determine mRNA delivery and transfection efficiency. Their acid dissociation constant (pKa) determines the ionization behavior and surface charge of LNPs, further affecting their stability and toxicity. Helper lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), envelope the lipid–mRNA complex, thereby ensuring LNP stability. Cholesterol regulates membrane fluidity by filling gaps between phospholipids. PEG–lipids improve particle stability, reduce particle binding to plasma proteins in vivo, and prolong the systemic circulation time. Additionally, PEG–lipids protect the LNPLipid nanoparticles (LNPs) are the most commonly used delivery vectors for messenger RNA (mRNA) in clinical applications. They protect mRNA from degradation, enhance cellular uptake, and facilitate cytoplasmic release. LNPs have high drug-loading capacity, high encapsulation efficiency, sustained release, high stability, low toxicity, and enhanced efficacy. Three nucleic acid medicines based on LNPs have been approved, including Patisiran, BNT162b2, and mRNA-1273. These applications demonstrate the success of LNP delivery systems for gene drugs and vaccines. The momentum of preclinical research and clinical trials for mRNA–LNP drugs is increasing. However, the current focus is predominantly on liver delivery, leading to a prevalence of liver-targeted delivery among LNPs. DLin-MC3-DMA (MC3) LNPs are the most representative vector for liver-targeted delivery. Both SM-102 and ALC-0315 are MC3 LNPs that primarily deliver mRNA to the liver after intravenous injection. However, LNPs for extrahepatic-targeted mRNA delivery are still in the early stages of development. To fully utilize the advantages of mRNA technology, such as its low cost, high efficiency, and short developmental cycles, the development of an extrahepatic-targeted delivery strategy for mRNA–LNPs is of great significance. Current research is focused on enhancing the accuracy of mRNA–LNP delivery to specific cells, tissues, or organs to improve the therapeutic effect and minimize potential side-effects. In this review, we summarize the latest strategies for the targeted delivery of mRNA–LNPs to cells and tissues, including tissue-specific or cell-specific LNPs, following different injection modes. The review also highlights the preclinical and clinical research progress of mRNA–LNPs in the treatment of cancer, infectious diseases, and hereditary diseases. Finally, the current challenges and potential future research directions are briefly reviewed. LNPs are composed of ionizable cationic lipids (ICLs), helper lipids, cholesterol, and polyethylene glycol (PEG) lipids. ICLs are key factors that determine mRNA delivery and transfection efficiency. Their acid dissociation constant (pKa) determines the ionization behavior and surface charge of LNPs, further affecting their stability and toxicity. Helper lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), envelope the lipid–mRNA complex, thereby ensuring LNP stability. Cholesterol regulates membrane fluidity by filling gaps between phospholipids. PEG–lipids improve particle stability, reduce particle binding to plasma proteins in vivo, and prolong the systemic circulation time. Additionally, PEG–lipids protect the LNP