<p>Immunotherapy has become an indispensable modality in the treatment of cancer, yet challenges such as resistance and substantial variability in therapeutic responses among patients remain significant obstacles. Key technologies, including spatial omics, have emerged as critical methods for exploring the complex tumor microenvironment. Increasing evidence suggests that, compared to single-cell sequencing, spatial omics technologies offer the advantage of preserving spatial context and integrating multimodal analyses, thereby advancing our understanding of complex interactions within biological tissues. In this perspective article, we present a comprehensive overview of the origins, classifications, and characteristics of various modalities of spatial omics analyses. Furthermore, we discuss the heterogeneity of the TME in the spatial context, such as the phenotypic differences between B cells and T cells near normal versus tumorous tissues—where they predominantly express immune-suppressive receptors in proximity to the tumor. Additionally, we summarize the applications of spatial omics in different cancer therapies, recent advancements in exploring cellular interactions and tertiary lymphoid structures, and the challenges faced in clinical translation. In light of these findings, we advocate for a broader application of spatial omics, combined with other technologies, as this will unveil overlooked therapeutic targets and could potentially realize precision immunotherapy for cancer.</p>