Background <p>There is limited evidence regarding the influencing factors associated with diverse types of spiritual needs in patients with terminal cancer. To investigate the spectrum of spiritual needs in patients with terminal cancer and clarify the impact of cancer -related pain, fatigue, sociodemographic characteristics on these needs.</p> Methods <p>This cross-sectional study was designed in accordance with the STROBE guidelines. Participants (<i>N</i> = 224) were recruited from three tertiary class A medical centers in southern China via convenience sampling. Socio-demographic, clinical profiles, spiritual needs, pain and fatigue were assessed. Univariate and multivariate analyses were performed using standardized statistical methods.</p> Results <p>Multiple linear regression analysis revealed that religious affiliation, residence, healthcare payment method, pain properties and number of pain sites significantly predicted the overall spiritual needs of patients with terminal cancer (F = 6.972, <i>p</i> &lt; 0.001; Durbin-Watson statistic = 1.642; adjusted <i>R</i>² = 0.337).&#xa0;Subgroup analyses demonstrated distinct predictors for specific spiritual domains:&#xa0;pain severity predicted needs for love and connection and hope and peace, while pain properties and multifocal pain influenced meaning and purpose and overall spiritual needs (<i>p</i> &lt; 0.001; adjusted R² range: 0.273–0.386).</p> Conclusion <p>Religious affiliation and healthcare payment method emerged as prominent predictors of diverse spiritual needs in the analysis. Pain severity and multifocal pain differentially influenced specific spiritual domains. Although this study attempts to identifies patterns in spiritual needs, individual variability persists. These findings underscore the necessity of personalized spiritual care in hospice settings, tailored to the content and intensity of each patient's unique needs.</p>