AbstractCancer immunotherapy has appeared as a prospective therapeutic modality. Therapeutic antibodies induced in an in vitro expression system act as “targeting missiles” against tumor‐associated binding sites, and subsequently, immune system attack on tumors is restored or boosted. These antibody regimens are engineered towards enhanced Fc efficacy, humanization, and fragmentation to specifically recognize and bind to effective tumor‐associated targets. The challenge lies in obtaining efficient therapeutic regimens with low response rates, acquisition of resistance, and immune‐related undesirable effects of artificially designed therapeutic antibodies, which is crucial for enhancing clinical efficacy. This review provides an in‐depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints, co‐stimulatory receptors, and extracellular membrane receptors. It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets. The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities. Understanding antibody sources, ongoing evaluation of engineered antibodies, and tumor‐associated antigen research pave the way for designing appropriate antibody‐based immunotherapy regimens.