Mantle cell lymphoma (MCL) and Burkitt lymphoma (BL) are aggressive lymphoid malignancies with distinct molecular features and variable treatment outcomes. The transcription factor, SOX11 is atypically expressed in the majority of MCL cases and a subset of BL, and has emerged as a key regulator of gene expression and tumor biology. Recent findings identified SAMHD1, a dNTPase involved in nucleotide metabolism and DNA repair, as a novel interacting partner of SOX11. This thesis explores the structural and functional dynamics of the SOX11–SAMHD1 interaction using a multidisciplinary approach integrating transcriptomics, proteomics, computational modeling, and molecular validation. RNA-seq analysis of SOX11-expressing BLcell lines revealed over 5,600 differentially expressed genes, with significant enrichment for DNA damage response and immune regulation pathways. Proteomic profiling of MCL cell lines identified 51 high-confidence SOX11-binding proteins involved in RNA splicing and nuclear structure, with SAMHD1 among the top candidates. Molecular docking using HADDOCK predicted a stable electrostatically-driven interaction interface between SOX11 and SAMHD1, which was further characterized by PDBsum analysis. Native gel electrophoresis demonstrated that SOX11 impairs SAMHD1 tetramerization in MCL cells, but not in BL cells, corroborating the context-specificity of this interaction. Proximity ligation assays confirmed nuclear co-localization of SOX11 and SAMHD1 only in MCL models, but not in BL. These findings suggest broader roles for SOX11 in RNA processing and genome stability. This work offers novel insights into the molecular pathology of lymphoid malignancies and proposes the SOX11–SAMHD1 axis as a targetable vulnerability in precision oncology.