Purpose <p>Patients with advanced cancer endure considerable physical and emotional distress without sufficient supportive care. This cross-sectional study examined the relationship between cancer-related symptoms, supportive care needs, and distress levels in patients with advanced lung, head and neck, or gastrointestinal cancers.</p> Methods <p>158 patients were assessed for symptom burden and distress levels using the M.D. Anderson Symptom Inventory (MDASI) and unmet needs using the Supportive Care Needs Survey (SCNS-34) within one month of treatment initiation. Pearson correlations and multiple regression analyses were used to explore associations between supportive care needs and distress.</p> Results <p>Distress levels were moderate across the study population, with fatigue, pain, and disturbed sleep being the most reported symptoms. Patients who lived with their caregivers reported significantly lower needs in four out of five domains. Positive correlations were found between distress levels and supportive care needs in the psychological (<i>r</i> = 0.342, <i>p</i> &lt; 0.001), health system (<i>r</i> = 0.253, <i>p</i> = 0.001), patient care and support (<i>r</i> = 0.237, <i>p</i> = 0.003), and physical and daily living domains (<i>r</i> = 0.378, <i>p</i> &lt; 0.001). Multiple regression analysis showed that these domains collectively explained a significant portion of the variance in distress levels (R2 = 0.169, <i>p</i> &lt; 0.001).</p> Conclusion <p>Independent of demographic or clinic characteristics, patients with advanced cancer experience moderate distress and unmet supportive care needs, particularly in psychological and health system domains. The association between living with caregivers and lower reported needs suggests that caregiver support may play a crucial role in meeting these needs. Therefore, integrating strategies that involve and support caregivers could potentially reduce distress and improve the quality of life for patients with advanced cancer.</p>