Effective treatment strategies for second-line therapy in extensive-stage small cell lung cancer (ES-SCLC) are currently lacking. For this reason, we collected and recorded efficacy and safety data from patients with ES-SCLC who had disease progression after first-line treatment and received albumin-bound paclitaxel, anlotinib, and immunotherapy. Preliminary data showed an objective response rate of 37.78%. Median progression-free survival and overall survival were 5 months and 10 months, respectively. Treatment-related adverse events were mostly tolerable. Subgroup analysis indicated that efficacy correlated with the interval from last chemotherapy to treatment initiation and specific drug-related adverse events. Further analysis of immune cell subtypes suggested that the mechanism may involve depletion of immune suppression to activate immune responses synergistically against tumors. With its promising efficacy and manageable adverse effects, this regimen holds potential as a significant option for second-line therapy in ES-SCLC. However, due to the limited sample size, further clinical validation is needed to ascertain its true clinical value.