The lipid-coated mesoporous silica nanoparticles (LMSNs) that can synergistically harness the advantages and mitigate the disadvantages of the liposomes and MSNs are considered potential drug carriers. So far, several methods have been developed to prepare LMSNs, including vesicle fusion, thin-film hydration, and solvent exchange. Despite their wide application in LMSN preparation, these methods are short of detailed elaboration and comparison, which hinders their further development. In this review, for the first time, the three methods are systematically summarized, including their mechanisms, influence factors, advantages, and limitations. Although these methods are all based on lipid self-assembly, there is still a difference between them. In order to efficiently prepare LMSNs, we proposed that a suitable method should be selected based on the actual situation. It is conceivable that the elaboration and comparison in this review will make these methods easy to be understood and provide guidance for the design of LMSNs as drug carriers.