In the context of extensive-stage small-cell lung cancer (ES-SCLC), the optimal choice of second-line treatment following standard-of-care first-line platinum-based chemoimmunotherapy and maintenance immunotherapy is not clearly defined. Making therapeutic decisions requires careful consideration of various factors, including the choice of first-line treatment, the treatment-free interval (TFI) after first-line chemotherapy (whether the disease is platinum-sensitive or platinum-resistant), performance status, therapy-related toxicities, and contraindications. This program offers case studies presented by expert faculty to illustrate how the latest evidence and guidelines can be incorporated to personalize second-line treatment plans for patients with ES-SCLC.