The occurrence and progression of tumors can be established through a complex interplay between tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors, and immune cells. This study utilized single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to assess the pseudotime trajectory and spatial interactive relationship between EMT invasive malignant tumors and immune cells in primary CRC tissues at different stages (stage I/II and stage III with tumor deposit). The research characterized the spatiotemporal relationship between invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, using evolution trajectory and EMT-invasion genes. Strikingly, The invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These cell types are adjacent to the EMTPs and are linked to beneficial EMT invasion genes, particularly C-X-C motif ligand 1 (CXCL1) and CXCL8 which are important for prognosis. Interestingly, the EMTPs for stage I mainly produce an inflammatory pre-invasive niche, while the EMTPs for stage III tissues are likely to produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor progression and formation in CRC. This study provides a framework for studying the spatiotemporal pre-invasive niche of different stages in CRC samples.