AbstractBackgroundSingle‐cell transcriptomics has revolutionised our understanding of the cellular composition of the tumour microenvironment (TME) in nasopharyngeal carcinoma (NPC). Despite this progress, a key limitation of this technique has been its inability to capture epithelial/tumour cells, which has hindered further investigation of tumour heterogeneity and immune escape in NPC.MethodsIn this study, we aimed to address these limitations by analysing the transcriptomics and spatial characteristics of NPC tumour cells at single‐cell resolution using scRNA/snRNA‐seq and imaging mass cytometry techniques.ResultsOur findings demonstrate multiple patterns of immune escape mechanisms in NPC, including the loss of major histocompatibility complex (MHC) molecules in malignant cells, induction of epithelial–mesenchymal transition in fibroblast‐like malignant cells and the use of hyperplastic cells in tumour nests to protect tumour cells from immune infiltration. Additionally, we identified, for the first time, a CD8+ natural killer (NK) cell cluster that is specific to the NPC TME.ConclusionsThese findings provide new insights into the complexity of NPC immune landscape and may lead to novel therapeutic strategies for this disease.