Background: Most cancer patients' families suffer from maladaptation which increases family distress and caregiving burden. This study was conducted to explore the relationship between these maladaptation indicators, and the sense of coherence (SOC) of family caregivers alongside other family resilience determines among family caregivers of cancer patients. Methods: A total of 104 family caregivers of cancer patients were included in this cross-sectional study. They answered three questionnaires to assess family resilience factors: Family Inventory of Resources for Management (FIRM), Family Crisis Oriented Personal Evaluation Scales (F-COPES), and SOC scale. In addition, family maladaptation factors were determined by two instruments, including Family Distress Index (FDI) and Caregiver Burden Inventory (CBI). Results: The results of this study showed that the FIRM and the SOC together were responsible for 35% and 43% of the variances in FDI and CBI scores, respectively (P < 0.001). "Reframing", the subscale of the F-COPES, significantly predicted the variances of FDI (β = −0.26, P = 0.01) and CBI scores (β = −0.21, P = 0.04). Moreover, "Mastery and health", the subscale of the FIRM, significantly predicted the variances of FDI (β = −0.38, P < 0.01) and CBI scores (β = −0.21, P = 0.02). Conclusions: Family caregiver's SOC alongside other family resilience determinants plays a significant role in alleviating family distress and caregiver burden. It is suggested that palliative care providers consider family caregivers' SOC in developing a psychological intervention plan to improve family resilience in families of cancer patients.