Cancer progression and treatment failure are profoundly influenced by the complex ecosystem of tumors, characterized by extensive cellular heterogeneity and a spatially organized microenvironment. Single-cell sequencing has revealed unprecedented diversity in malignant, immune, and stromal tumor populations, but lacks anatomical context. In contrast, spatial transcriptomics can map gene expression within tissue architecture, but typically at low cellular resolution. Integrative approaches now merge these advantages, enabling precise characterization of clonal dynamics, cellular communication, and the ecological niches that underlie metastasis and therapeutic resistance. This integrative approach provides a multidimensional view of tumor biology, highlighting context-dependent mechanisms of drug vulnerability and immune evasion. In this review, we explore how single-cell and spatial technologies are reshaping our understanding of the cancer ecosystem, integrating these two advanced technologies and advancing our progress toward spatially based precision oncology.

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