Abstract: Due to their excellent biocompatibility, low toxicity, and minimal immunogenicity, liposomes have been extensively utilized for the efficient delivery of antitumor agents, antimicrobial agents, among many others. However, despite the advancement in liposome technologies, the in vivo behaviors of liposomes remain insufficiently understood, posing significant challenges to their clinical translation and application. A comprehensive understanding of the processes involved in blood circulation, biodistribution, metabolism, and excretion of liposomal therapeutics—along with a thorough elucidation of the underlying regulatory mechanisms and potential 'composition-efficacy' relationships—would greatly aid in the rational design of liposome-based therapies. This review provides an overview of the in vivo delivery processes, influencing factors, and regulatory strategies of liposomal drugs, serving as reference for future research in the field.