Background: Global demographic transition and the rising prevalence of advanced chronic diseases necessitate care paradigms centered on the palliative dyad. Family caregivers face significant physical and existential burden, often manifesting as anticipatory grief and spiritual distress. While spirituality is a pillar of palliative care, evidence on specific nursing interventions and validated assessment tools for caregivers remains fragmented. This systematic review aims to determine the effectiveness of nursing interventions on the spiritual well-being of family caregivers and to identify validated instruments for assessing their spiritual needs. Methods: Following JBI and PRISMA 2020 guidelines (PROSPERO: CRD420251166271), a systematic search was conducted in MEDLINE, CINAHL, Web of Science, and Scopus (2019–2025). Methodological quality was appraised using the Mixed Methods Appraisal Tool (MMAT). Results: Preliminary screening yielded 482 records, with 34 studies meeting criteria for full-text analysis. Initial findings suggest interventions into psycho-spiritual counseling and compassionate presence frameworks. While the FACIT-Sp and the Herth Hope Index are prevalent in international literature, there remains a significant scarcity of instruments that have undergone rigorous cross-cultural validation for diverse populations of family caregivers. Conclusion: These interventions provide a framework for humanized nursing praxis, addressing the spiritual “fourth pillar” to enhance dignity and satisfaction with care within the palliative dyad.