Background/Objectives: This systematic review aimed to comprehensively evaluate the role of spirituality and religion in the journey of patients with cancer and assess their impact on various aspects of well-being and coping mechanisms. Methods: Systematic searches were conducted in PubMed, Scopus, and Google Scholar following the PRISMA guidelines. This study focused on the period from 2014 to 2024, the time chosen for the emerging integration of spirituality and religion in cancer treatment. Inclusion criteria targeted studies exploring the impact of spirituality and religion on cancer patients’ quality of life, coping, and treatment outcomes. Results: A comprehensive search initially yielded 2591 papers, of which 1544 were excluded as duplicates, and 113 were further excluded based on the inclusion criteria. Ultimately, 53 papers were selected for review, including 8 prospective cohort, 17 cross-sectional, 16 observational descriptive, and 12 RCT studies. Encompassing 13,590 patients with various cancer types, including breast, gastrointestinal, prostate, brain, and others, the review highlighted spirituality and religion’s significant role in improving cancer patients’ well-being. Across different cancers, greater spiritual well-being and religious coping were consistently associated with an improved quality of life, reduced distress, enhanced coping, and better treatment outcomes. Interventions such as mindfulness therapy, yoga, and religious coping strategies positively impact patients’ spiritual and emotional well-being. Conclusions: This review highlights the vital role of spirituality and religion in cancer care. Integrating these aspects into patient plans offers comfort and support throughout treatment. Healthcare providers should prioritize spiritual support to enhance patient well-being and optimize outcomes.