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Cancer profoundly impacts patients’ psychological well-being, yet comprehensive synthesis regarding mental health symptoms and contributing psychosocial factors remains limited. This systematic review synthesizes global evidence published between 2000 and 2023 on the psychological outcomes experienced by cancer patients and their associated clinical and psychosocial drivers. Conducted in accordance with PRISMA 2020 guidelines, electronic searches across PubMed, ScienceDirect, and Google Scholar yielded 24 eligible studies (23 peer-reviewed articles and one dissertation) in English and Turkish. Due to methodological heterogeneity, data were integrated using a narrative synthesis. Results revealed that depression, anxiety, general distress, adjustment disorders, post-traumatic stress symptoms, fear of recurrence, and social isolation are highly prevalent throughout the continuum of care. Crucially, cancer-related stigma identified as a major psychosocial determinant, significantly compounding depressive symptoms, body image disturbance, reduced self-esteem, and social withdrawal. Furthermore, unaddressed distress directly impaired treatment adherence, coping mechanisms, and overall quality of life. These findings highlight that psychological assessment must be routinely integrated into standard multidisciplinary oncology care to enable early detection and targeted intervention. Future research should prioritize longitudinal methodologies and standardized evaluation tools to track symptom trajectories and test intervention efficacy.