Purpose <p>Cancer profoundly affects patients’ physical and psychological well-being, yet spiritual pain remains underexplored within supportive oncology care. This study examined relationships between spiritual pain, physical pain, and existential well-being among Iranian cancer patients.</p> Methods <p>In a cross-sectional descriptive-correlational design, 147 cancer patients were recruited via convenience sampling from oncology settings in Iran. Participants completed the Groves and Klauser Spiritual Pain Scale, the Ellison and Paloutzian Existential Well-Being Scale, and a physical pain questionnaire. Data were analyzed using descriptive statistics and correlation analyses in SPSS.</p> Results <p>Over half of participants reported moderate spiritual pain; the majority had average existential well-being, and 40% reported no physical pain. Spiritual pain correlated negatively with existential well-being (<i>r</i> = –0.58, <i>p</i> &lt; 0.001), while physical pain correlated positively with spiritual pain (<i>r</i> = 0.20, <i>p</i> = 0.01), indicating that higher physical discomfort is associated with greater spiritual distress.</p> Conclusions <p>The findings reveal a significant interplay between spiritual pain, physical pain, and existential well-being in cancer patients, underscoring the importance of spiritual distress as part of the symptom burden. Integrating spiritual care into oncology practice may enhance supportive care beyond physical symptom management.</p>