In the past, there was no second-line chemotherapeutic agent suitable for use when urothelial carcinoma (UC) progressed to platinum-resistant UC. However, recently, several new treatment options, such as immune checkpoint inhibitors or targeted therapy have shifted the treatment paradigm regarding second-line therapeutic modalities. A novel class of therapeutic agents includes an antibody-drug conjugate (ADC). ADCs consist of three characteristics: a monoclonal antibody, linker, and payload. The specificity of the monoclonal antibody facilitates the delivery of a linked cytotoxic drug directly into the target tumor cell. Although various ADCs have been developed and approved for use in treating several solid tumors, almost all ADCs for the treatment of UC are still in the testing phase. Here, we review the key points about ADCs and summarize the novel ADCs that are approved or are involved in ongoing studies in UC.