Following the breakthroughs of CAR T cells in the treatment of several hematological malignancies, clinical trials based on genetically modified immune cells are exponentially increasing. Redirecting T cell cytotoxicity against solid tumors via CARs, however, encountered several barriers that require the engineering of additional functions to improve safety, migration, efficacy, and persistence in solid tumors. Complementary strategies tried to harness macrophage properties such as cancer cell phagocytosis, cytokine release, and antigen presentation to induce broader antitumorigenic immune response. While providing a comprehensive overview on the latest technologies in the cell-based immunotherapy realm, we propose that engineering synthetic interplay between immune cells will be the next breakthrough to drive safer and more effective living therapeutics.