Background: Recent studies have identified solute carrier family 19 member 1 (SLC19A1) as a second messenger transporter that regulates massive immune-related signaling cascades, but current studies provide limited information. This study aims to evaluate its role and the potential mechanisms across various cancers. Methods: We analyzed multi-omics data from a pan-cancer cohort to evaluate SLC19A1 expression and its association with multiple features, including prognosis, tumor stemness, genome instability, and immune infiltration. Immunofluorescence staining was performed to validate SLC19A1 expression in tumor tissues and its relationship M2 macrophages. In addition, we used web tools such as ROCplotter to evaluate the association between SLC19A1 and response to chemotherapy and immunotherapy. Results: SLC19A1 was found to be overexpressed in multiple cancer types compared to normal tissues, correlating with poor prognosis. High SLC19A1 levels were associated with increased genomic instability and immune suppression. In addition, SLC19A1 was negatively correlated with CD8+ T-cell infiltration and positively correlated with M2 macrophage infiltration. The association of SLC19A1 with M2 macrophages was confirmed in multiple immunofluorescence staining. Finally, SLC19A1 was associated with the response to chemotherapy and immunotherapy in a variety of tumors. Conclusions: Our findings position SLC19A1 as a novel unfavorable prognostic marker in cancer, closely linked to immune suppression and genomic instability. This study highlights the need for further exploration of SLC19A1 as a therapeutic target and its implications in cancer treatment strategies.