Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown significant potential in cancer therapy due to its ability to selectively induce apoptosis in tumor cells while minimally affecting normal cells. Currently, developed TRAIL-based cancer therapies have demonstrated better therapeutic effects in preclinical trials. However, their clinical application has been limited by issues such as poor stability, insufficient targeting, short half-life in vivo, and low bioavailability. In recent years, nanocarriers, including liposomes, nanoparticles, and micelles, have been widely utilized in the field of drug delivery. Combining TRAIL with these nanocarriers can help overcome these limitations and enhance its antitumor efficacy. This review summarizes the latest research progress on the combination of TRAIL with liposomes, nanoparticles, and micelles in cancer treatment. It explores the mechanisms by which these nanocarriers improve the stability, targeting, and bioavailability of TRAIL, as well as the therapeutic advancements of this combined approach at both the animal and clinical levels. The aim is to provide valuable insights for the development and clinical application of TRAIL-based cancer therapies.