Fetal-like vascular remodeling and endothelial anergy are common features linked to the development of immune tolerance in various solid tumors. This study investigates how anti-angiogenic therapy affects immune checkpoint blockade (ICB) responses in advanced, therapy-resistant nasopharyngeal cancer (NPC). We generated a longitudinal, single-cell, spatial transcriptomic atlas of NPC patients treated with Bevacizumab (anti-VEGF) and Pembrolizumab (anti-PD1) in order to define “cell-state alterations” in the tumor ecosystems of responders versus non-responders. Clinical outcome data obtained from the Phase II open-labelled randomized study suggested that patients treated with a combination of anti-VEGF and anti-PD1 had higher ORR (50.0% vs 12.5%, p=0.003), and longer median PFS (18.5 vs. 1.6 months, p<0.001) than those treated with immunotherapy alone. Our scRNA-seq and spatially-resolved transcriptomic analysis of longitudinal treatment samples demonstrate that anti-angiogenic therapy alone can induce remarkable cell-state alterations and reorganize spatial niches within the tumor microenvironment (TME), priming the ecosystem to enhance immunotherapy response.