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Invasive fungal infections (IFIs) are life-threatening complications in immunocompromised patients, particularly those with hematologic malignancies or undergoing transplantation. Despite advances in diagnostic methods and antifungal therapy, IFI-related mortality remains unacceptably high. Evidence from Latin America is scarce, limiting the understanding of regional epidemiology and outcomes. Our work aimed to analyze the epidemiological and clinical profiles of pediatric hemato-oncologic patients diagnosed with proven IFIs. We conducted a retrospective, cross-sectional study by reviewing medical records of patients diagnosed with proven IFIs according to the 2020 criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group, at the Hospital Universitario "Dr. José Eleuterio González" in northeast Mexico, between 2018 and 2024. Statistical analysis included descriptive and inferential methods. A p-value < 0.05 was considered statistically significant. Thirty-three patients were included (mean age 6 years; 54.5% male). Most (91%) were classified as high risk for IFIs, and acute lymphoblastic leukemia was the most frequent underlying malignancy (72.7%). Mold infections accounted for 69.7% of cases, mainly Aspergillus spp. and Fusarium spp., while Candida tropicalis was the most common yeast. The sinonasal region was the predominant site of mold disease. Prophylaxis was administered in 69.7% of patients, most commonly with itraconazole. Amphotericin B was the primary therapeutic agent, alone or in combination with voriconazole, and 42.4% required surgical intervention. Overall mortality was 21.2%, higher in yeast infections (30%) compared with molds (17.4%). Intensive care unit admission was the only independent predictor of death (OR 35.4; p = 0.019). In pediatric hemato-oncologic patients, IFIs were predominantly associated with acute lymphoblastic leukemia, neutropenia, and induction chemotherapy. Mold infections accounted for most cases, and mortality remained high despite prophylaxis. These findings provide novel data from Latin America, where studies on pediatric IFIs are limited, and underscore the need for improved diagnostic and preventive strategies in high-risk populations.