<p>This study employed a serial multiple mediator model to examine the mediating effects of coping strategies (adaptive and maladaptive) and psychological distress on the relationship between resilience and general well-being in cancer patients. A cross-sectional study was conducted with 551 participants diagnosed with cancer recruited from the two cancer hospitals in India. The serial mediator model was applied to elucidate the serial causality between two mediators: coping and psychological distress. This analysis, utilizing the PROCESS macro program within SPSS, explored direct and indirect effects. The results revealed a significant total effect in the theoretical serial mediation model of resilience, coping strategies (adaptive and maladaptive), psychological distress, and general well-being (coefficient <i>c</i> = 1.583, SE = 0.038, <i>p</i> &lt; 0.001). The overall study findings confirmed that strengthening resilience can help cancer patients improve their well-being by providing them with effective (adaptive) coping strategies to decrease the psychological distress.</p>