This review highlights the role of lipid-based nanosystems (LNS) in advancing cancer immunotherapy. LNS, including liposomes, lipid nanoparticles (LNPs), and solid lipid nanoparticles (SLNs), have emerged as promising carriers due to their favorable physicochemical properties and specific applications in delivering immunotherapeutic agents. The review discusses the challenges faced by immunotherapy, such as off-target effects, limited activity, and low local accumulation, and how LNS can address these issues through enhanced delivery, direct modulation of the immune system, and targeting of the immunosuppressive tumor microenvironment (TME). Key advancements in LNS include their ability to deliver various types of agents, including hydrophobic and hydrophilic drugs, antibodies, and nucleic acids. This versatility allows for synergistic effects of multiple therapeutic agents, enhancing the efficacy of immunotherapy. LNS can also improve the pharmacokinetics of payloads by reducing clearance rates and protecting them from degradation, thereby widening the therapeutic window. In the context of immune checkpoint inhibition (ICI) therapies, LNS have been used to enhance the accumulation of ICIs in tumor regions and reduce toxicities. Surface decoration of ICIs on LNS can target specific tumor cells or features, improving the specificity and effectiveness of therapy. Additionally, LNS can deliver cytokines like IL-2, IL-12, and IL-15 to enhance T cell function, and they can be used to engineer T cells in vitro and in vivo, improving their specificity and anti-tumor activity. The review also explores the use of LNS in targeting the TME, particularly in modulating the interactions between immune cells, stromal cells, and tumor cells. Strategies include reversing inhibitory signals in innate immune cells, sensitizing tumor cells, and targeting stromal cells to remodel physical barriers in drug delivery. Combining these approaches with other modalities like photodynamic therapy (PDT) and chemotherapy can further enhance the synergistic effects. Finally, the review discusses the clinical applications of LNS in cancer immunotherapy, including cancer vaccines, gene delivery, and cytokine therapies. It highlights the ongoing clinical trials and the potential of LNS to improve the efficacy and precision of immunotherapies, making them a crucial component in the next generation of anti-tumor treatments.This review highlights the role of lipid-based nanosystems (LNS) in advancing cancer immunotherapy. LNS, including liposomes, lipid nanoparticles (LNPs), and solid lipid nanoparticles (SLNs), have emerged as promising carriers due to their favorable physicochemical properties and specific applications in delivering immunotherapeutic agents. The review discusses the challenges faced by immunotherapy, such as off-target effects, limited activity, and low local accumulation, and how LNS can address these issues through enhanced delivery, direct modulation of the immune system, and targeting of the immunosuppressive tumor microenvironment (TME). Key advancements in LNS include their ability to deliver various types of agents, including hydrophobic and hydrophilic drugs, antibodies, and nucleic acids. This versatility allows for synergistic effects of multiple therapeutic agents, enhancing the efficacy of immunotherapy. LNS can also improve the pharmacokinetics of payloads by reducing clearance rates and protecting them from degradation, thereby widening the therapeutic window. In the context of immune checkpoint inhibition (ICI) therapies, LNS have been used to enhance the accumulation of ICIs in tumor regions and reduce toxicities. Surface decoration of ICIs on LNS can target specific tumor cells or features, improving the specificity and effectiveness of therapy. Additionally, LNS can deliver cytokines like IL-2, IL-12, and IL-15 to enhance T cell function, and they can be used to engineer T cells in vitro and in vivo, improving their specificity and anti-tumor activity. The review also explores the use of LNS in targeting the TME, particularly in modulating the interactions between immune cells, stromal cells, and tumor cells. Strategies include reversing inhibitory signals in innate immune cells, sensitizing tumor cells, and targeting stromal cells to remodel physical barriers in drug delivery. Combining these approaches with other modalities like photodynamic therapy (PDT) and chemotherapy can further enhance the synergistic effects. Finally, the review discusses the clinical applications of LNS in cancer immunotherapy, including cancer vaccines, gene delivery, and cytokine therapies. It highlights the ongoing clinical trials and the potential of LNS to improve the efficacy and precision of immunotherapies, making them a crucial component in the next generation of anti-tumor treatments.