Abstract
Gastric cancer (GC) is plagued by profound intratumoral heterogeneity and a complex tumor microenvironment (TME), which are the core obstacles to precise diagnosis and treatment. Conventional bulk multi-omics technologies average molecular signals across tissues, thus masking cellular heterogeneity; single-cell multi-omics resolves cellular diversity but dissociates cells from their native spatial context, leading to the loss of critical information on intercellular crosstalk and molecular spatial distribution. These limitations result in an incomplete understanding of GC pathogenesis and TME regulatory networks. Spatial multi-omics technologies, integrating genomics, transcriptomics, proteomics, and metabolomics with high-resolution spatial localization, address these key scientific problems by preserving the native tissue architecture and elucidating the spatiotemporal dynamics of molecular and cellular events in GC. This review systematically synthesizes the latest advances in the application of four major spatial multi-omics modalities in GC research over the past 15 years, with a critical evaluation of the technical performance, methodological shortcomings, and clinical translation potential of existing studies. Unlike previous reviews that only summarize research findings, this work uniquely integrates technical principles, mechanistic discoveries, and clinical translation of spatial multi-omics in GC, deeply analyzes the practical barriers to clinical application, and systematically elaborates the integration of spatial multi-omics with artificial intelligence (AI). We also identify unresolved challenges in the field and propose future development directions, providing a comprehensive and in-depth reference for the advancement of GC precision medicine based on spatial multi-omics.