The article reviews the advancements in single-cell RNA sequencing (scRNA-seq) in understanding melanoma heterogeneity and treatment resistance. Over the past decade, significant improvements have been made in melanoma treatment, but intratumoural heterogeneity (ITH) remains a challenge, contributing to treatment resistance. ITH is driven by the plasticity of melanoma cells and the diverse stromal and immune cell types in the tumour microenvironment (TME). ScRNA-seq has revealed the existence of multiple phenotypic and transcriptional cell states within the same tumour, including differentiated and dedifferentiated melanoma cells, and diverse immune cell subsets. These findings highlight the complexity of melanoma and the need for personalized treatment approaches. ScRNA-seq has also elucidated mechanisms of tumour progression, treatment response, and resistance, providing insights into how melanoma cells adapt and acquire resistance. The review discusses the challenges and future directions of scRNA-seq, emphasizing the importance of integrating multiomics data and spatial transcriptomics to better understand and address treatment resistance in melanoma.The article reviews the advancements in single-cell RNA sequencing (scRNA-seq) in understanding melanoma heterogeneity and treatment resistance. Over the past decade, significant improvements have been made in melanoma treatment, but intratumoural heterogeneity (ITH) remains a challenge, contributing to treatment resistance. ITH is driven by the plasticity of melanoma cells and the diverse stromal and immune cell types in the tumour microenvironment (TME). ScRNA-seq has revealed the existence of multiple phenotypic and transcriptional cell states within the same tumour, including differentiated and dedifferentiated melanoma cells, and diverse immune cell subsets. These findings highlight the complexity of melanoma and the need for personalized treatment approaches. ScRNA-seq has also elucidated mechanisms of tumour progression, treatment response, and resistance, providing insights into how melanoma cells adapt and acquire resistance. The review discusses the challenges and future directions of scRNA-seq, emphasizing the importance of integrating multiomics data and spatial transcriptomics to better understand and address treatment resistance in melanoma.