<p>Low-grade gliomas (LGG) are malignant brain tumors that arise from the brain’s support cells (glial cells). LGG are the most common kind of central nervous system tumors in children and adolescents, accounting for around half of all cases. Tumor Protein p53 (<i>TP53</i>) regulates or promotes DNA damage and repair via a variety of cell cycle, apoptosis, and genomic stability pathways. However, the clinical role of <i>TP53</i> status in LGG patients is still unknown. Hence, we analyzed clinical data from the Cancer Genomic Atlas (TCGA) of LGG patients to see if <i>TP53</i> status affects clinical outcomes, molecular signatures of chemokines and microRNAs, and immune cell infiltrations within the tumor’s microenvironment of LGG patients. According to our findings, the most common phenotype in LGG patients is wild-type <i>TP53</i>, which is related to poor clinical outcomes and the expression of Chemokine ligand 14 (CXCL14) in many clinical parameters such as age, gender, stage, race, and purity. Besides, in LGG patients, wild-type <i>TP53</i> controls prognostic microRNAs such as has-miR-10a-3p and has-miR-155-5p. Furthermore, through activating GATA Binding Protein 3 (<i>GATA3</i>) and decreasing Fatty Acid Synthase (<i>FASN</i>), wild-type <i>TP53</i> orchestrates M1 macrophage and CD8⁺ T cell infiltration, as well as the formation of brown adipose tissue and decreased white adipose tissue. In this regard, the <i>TP53-CXCL14-GATA3</i> axis has the potential to predict poor clinical outcomes in patients with wild-type <i>TP53</i> LGG.</p>