The FAcilitates Chromatin Transcription (FACT) complex is a chromatin remodeler with emerging roles in cancer progression. This study utilizes a multi-omics strategy combining single-cell RNA sequencing (scRNA-seq), differential expression analysis, prognostic evaluation, and immune infiltration profiling to define the oncogenic functions of its subunits Structure-Specific Recognition Protein 1 (SSRP1) and SUPpressor of Ty 16 Homolog (SUPT16H). Experimental validation in liver and breast cancer cell lines confirms significant overexpression of both subunits, particularly in hepatocellular carcinoma. Single-cell analysis reveals FACT enrichment in malignant cell types and progressive upregulation along pseudotime. Elevated FACT expression correlates with an immunosuppressive tumor microenvironment marked by reduced cytotoxic immune cell infiltration. Drug sensitivity screening identifies FK866 as a potent inhibitor, and functional assays verify that its efficacy depends on FACT expression, as siRNA knockdown of SSRP1 and SUPT16H induced resistance. These results establish FACT as a critical oncogenic driver and a promising therapeutic target, providing insights for overcoming immune evasion and advancing precision oncology.