In addition to the naked therapeutic antibodies, next-generation therapeutic antibodies have recently attracted great attention. Examples of next-generation therapeutic antibodies include armed antibodies, such as antibody–drug conjugates (ADCs) and radioimmunotherapy (RIT), in which anticancer agents (ACAs) and radionuclides are conjugated, respectively, and bispecific antibodies (BsAbs), which are engineered hybrid antibodies with two different antigen-binding sites in a single molecule. Among these, ADCs have succeeded in demonstrating a strong clinical antitumor effect against naked therapeutic antibody-resistant cancer. More recently, we have focused on the bystander effect and immunogenic cell death (ICD) as novel types of mechanisms of action (MOAs) of ADCs. We have classified five modes of action of ADCs including (1) systemic circulation, (2) extravasation and intratumoral retention (passive targeting via EPR effect), (3) penetration within tumor tissue, (4) direct action on cells (active targeting, controlled drug release, and bystander effect), and (5) immune reactions. BsAbs, which can bind both tumor cells and T cells, are T-cell–dependent bispecific antibodies (TDBs). They have two types of MOAs: (1) immunological synapse–dependent cytotoxicity and (2) immunological synapse–independent cytotoxicity due to cytokines. The clinical application of alpha-RIT with shorter flight range and higher linear energy transfer activity over beta-RIT is expected to be useful when cells are resistant to conventional therapies. Currently, we have also proposed immune targeting as a novel drug delivery system concept. According to this concept, we are developing an anti–IL-7R ADC for the treatment of both lymphoid malignancy and autoimmune disease. In this review, while emphasizing the importance of DDS and molecular imaging, we will outline the development of therapeutic antibodies including next-generation types and introduce our relevant research works.