This chapter explores the mechanisms by which monoclonal antibodies (mAbs) exert cytotoxic effects on tumor cells, focusing on antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and immune checkpoint inhibition. It discusses the variable regions of antibodies blocking receptor-ligand interactions and the Fc region activating the immune system, leading to tumor cell destruction. The chapter also highlights the role of mAbs in targeting immune suppressive tumor microenvironments and the significance of specific mAbs like rituximab and trastuzumab in cancer therapy. The potential of antibody-drug conjugates (ADCs) in oncology is examined, emphasizing the evolution of mAb therapies and their growing clinical value. This chapter provides a comprehensive overview of mAb mechanisms in tumor immunity, underscoring the importance of these therapies in advancing cancer treatment strategies.