Background <p>Cancer immunotherapy boosts immune recognition of cancer cells via checkpoint inhibitors, monoclonal antibodies, and adoptive cell therapies. Although T cells, B cells, natural killer cells, and dendritic cells show promise, limitations such as immune evasion, inconsistent efficacy, and high costs persist. With their plasticity and tumor-homing abilities, macrophages offer an alternative. Engineered macrophages, through surface and genetic modifications, may enhance cancer treatment efficacy and precision.</p> Area covered <p>This paper examines macrophage-based cancer immunotherapy, highlighting engineering strategies to enhance therapeutic efficacy. Surface modifications, including nanoparticle-loaded macrophages, exosome nanocarriers, and membrane-coated systems, optimize drug delivery. Genetic engineering, such as CAR-macrophages, cytokine engineering, BiTE-based approaches, and CD47–SIRPα targeting, reprograms immune responses and overcomes tumor microenvironment (TME) challenges, and addresses the limitations and future prospects of macrophage therapy.</p> Expert opinion <p>Macrophage engineering holds great promise in cancer immunotherapy, enabling precise drug delivery, immune modulation, and TME reprogramming. Surface and genetic modifications enhance tumor targeting, phagocytic activity, and therapeutic efficacy. Despite challenges such as survival, retention, and off-target effects, optimizing macrophage-based therapies could revolutionize cancer treatment. Ongoing research is crucial to unlocking their full potential establishing engineered macrophages as a cornerstone of next-generation immunotherapies.</p>