The organ-specific immunosuppressive microenvironment of colorectal liver metastasis (CRLM) is a key cause of immunotherapy resistance. Based on single-cell RNA sequencing and spatial transcriptomics, we found that SPP1⁺ macrophages formed a functional axis with cancer-associated fibroblast (CAF) in CRLM foci, and constructed an immunosuppressive niche through metabolic reprogramming, extracellular matrix remodeling, and signal cross-talk. It is accompanied by myeloid cell expansion, T cell exhaustion, and up-regulation of immune checkpoint molecules. There are still core controversies and gaps in the current field: the developmental pathway of “Kupffer cell derivation” and “monocyte derivation” of SPP1⁺ macrophages is still controversial. The gap between the preclinical efficacy and clinical transformation of metabolic intervention needs to be urgently narrowed. The origin of TCR clonotypes of Tregs and the quantitative relationship between interleukin (IL-10) concentration gradient and CD8⁺ T cell depletion are still unclear. In view of the above mechanisms, this paper reviews the strategies such as precise targeting of immunosuppressive cells and synergistic metabolic-immune intervention, and prospects the direction of multi-omics guided individualized treatment, which provides theoretical support for overcoming the dilemma of immunotherapy for CRLM.