With the widespread adoption of checkpoint inhibitors as standard-of-care therapy for many cancers, the associated toxicities affecting multiple organ systems have become a significant limiting factor, particularly in select patient populations. Some organ-specific toxicities can be severe and life-threatening. Early recognition and prompt, effective management of these conditions are critical to improving patient care and ensuring the continued delivery of cancer therapy over the long term. Designed as a companion volume to our first handbook Managing Immunotherapy-Related Organ Toxicities published in 2022, this new book presents 65 unique and challenging cases involving toxicities across more than ten different organ systems. Each case includes a detailed clinical presentation, evaluation, treatment approach, and long-term patient outcome. The contributors are a group of leading experts from 14 centers worldwide, all of whom provide routine care for patients with complex toxicity conditions. This is the first book of its kind, Challenging Cases of Immunotherapy-Related Organ Toxicities, highlighting the real-world challenges physicians encounter in oncology clinical practice.