Purpose: The objective of our study is to propose fast, cost-effective, convenient, and effective biomarkers using the perfusion parameters from dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of immune checkpoint inhibitors (ICI) early response. Methods: The retrospective cohort used in this study included 63 patients with metastatic cancer eligible for immunotherapy. DCE-US was performed at baseline, day 8 (D8), and day 21 (D21) after treatment onset. A tumor perfusion curve was modeled on these three dates, and change in the seven perfusion parameters was measured between baseline, D8, and D21. These perfusion parameters were studied to show the impact of their variation on the overall survival (OS). Results: After the removal of missing or suboptimal DCE-US, the Baseline-D8, the Baseline-D21, and the D8-D21 groups included 37, 53, and 33 patients, respectively. A decrease of more than 45% in the area under the perfusion curve (AUC) between baseline and D21 was significantly associated with better OS (p = 0.0114). A decrease of any amount in the AUC between D8 and D21 was also significantly associated with better OS (p = 0.0370). Conclusion: AUC from DCE-US looks to be a promising new biomarker for fast, effective, and convenient immunotherapy response evaluation.