Antibody–drug conjugates (ADCs) are a promising cancer treatment that enables the targeted delivery of highly toxic payloads to tumours. However, their full potential is limited by challenges such as drug resistance, tumour heterogeneity, and treatment-related side effects. Emerging ADC formats, including bispecific ADCs, probody–drug conjugates (PDCs), immune-stimulating ADCs (ISACs), protein-degrader ADCs, and dual-drug ADCs, offer unique capabilities to address these challenges. For example, PDCs can enhance tumour specificity, while bispecific and dual-drug ADCs can combat resistance and heterogeneity. Integrating ISACs and protein-degrader ADCs with existing treatments may enable multimodal cancer therapy. Patient stratification and biomarker identification are crucial for maximizing clinical benefits. ADCs consist of a monoclonal antibody linked to a cytotoxic payload via a chemical linker. The antibody, linker, payload, and conjugation chemistry are key factors in ADC efficacy and safety. Current ADCs use humanized or fully human IgGs, with IgG1 being preferred for stability and immune cell engagement. Target selection is critical to minimize off-target toxicity, as many targets are expressed in nonmalignant tissues. Payloads are highly toxic, with sub-nanomolar or picomolar levels of cytotoxicity. Hydrophobic payloads can cause bystander effects but may also lead to toxicity and aggregation. Linkers must balance stability and efficacy, with cleavable linkers enabling efficient payload release in tumour cells. Homogeneity in ADCs is essential for consistent therapeutic outcomes. Site-specific conjugation methods, such as full alkylation of interchain disulfides or cysteine engineering, produce homogeneous ADCs with defined drug-to-antibody ratios (DARs). Bispecific ADCs, which target two antigens, can enhance tumour specificity and overcome resistance. Examples include MEDI4276 and ZW49, which target HER2 and show improved activity in preclinical models. However, clinical trials have shown variable efficacy and safety profiles. PDCs, which are conditionally active, can reduce off-target toxicity by remaining inactive until reaching the tumour microenvironment. They use protease-sensitive or pH-responsive masking moieties to activate upon tumour-specific conditions. Examples include CX-2029 and praluzatamab ravtansine, which target CD71 and CD166, respectively. These PDCs show promising antitumour activity with manageable toxicity. ISACs, which deliver agonists for pattern-recognition receptors (PRRs), can stimulate immune responses against tumour-associated DAMPs. They activate antigen-presenting cells (APCs) and other immune cells, leading to durable antitumour effects. ISACs with TLR7/8/9 agonists, such asAntibody–drug conjugates (ADCs) are a promising cancer treatment that enables the targeted delivery of highly toxic payloads to tumours. However, their full potential is limited by challenges such as drug resistance, tumour heterogeneity, and treatment-related side effects. Emerging ADC formats, including bispecific ADCs, probody–drug conjugates (PDCs), immune-stimulating ADCs (ISACs), protein-degrader ADCs, and dual-drug ADCs, offer unique capabilities to address these challenges. For example, PDCs can enhance tumour specificity, while bispecific and dual-drug ADCs can combat resistance and heterogeneity. Integrating ISACs and protein-degrader ADCs with existing treatments may enable multimodal cancer therapy. Patient stratification and biomarker identification are crucial for maximizing clinical benefits. ADCs consist of a monoclonal antibody linked to a cytotoxic payload via a chemical linker. The antibody, linker, payload, and conjugation chemistry are key factors in ADC efficacy and safety. Current ADCs use humanized or fully human IgGs, with IgG1 being preferred for stability and immune cell engagement. Target selection is critical to minimize off-target toxicity, as many targets are expressed in nonmalignant tissues. Payloads are highly toxic, with sub-nanomolar or picomolar levels of cytotoxicity. Hydrophobic payloads can cause bystander effects but may also lead to toxicity and aggregation. Linkers must balance stability and efficacy, with cleavable linkers enabling efficient payload release in tumour cells. Homogeneity in ADCs is essential for consistent therapeutic outcomes. Site-specific conjugation methods, such as full alkylation of interchain disulfides or cysteine engineering, produce homogeneous ADCs with defined drug-to-antibody ratios (DARs). Bispecific ADCs, which target two antigens, can enhance tumour specificity and overcome resistance. Examples include MEDI4276 and ZW49, which target HER2 and show improved activity in preclinical models. However, clinical trials have shown variable efficacy and safety profiles. PDCs, which are conditionally active, can reduce off-target toxicity by remaining inactive until reaching the tumour microenvironment. They use protease-sensitive or pH-responsive masking moieties to activate upon tumour-specific conditions. Examples include CX-2029 and praluzatamab ravtansine, which target CD71 and CD166, respectively. These PDCs show promising antitumour activity with manageable toxicity. ISACs, which deliver agonists for pattern-recognition receptors (PRRs), can stimulate immune responses against tumour-associated DAMPs. They activate antigen-presenting cells (APCs) and other immune cells, leading to durable antitumour effects. ISACs with TLR7/8/9 agonists, such as