This systematic review and meta-analysis evaluated the psychological outcomes of patients with rare cancers, including depression, anxiety, suicide, and post-traumatic stress disorder (PTSD), compared to healthy controls and common cancer patients. The study included 32 studies with 57,470 patients with rare cancers. The results showed a statistically significant increased risk of depression (RR = 2.61, 95% CI: 1.43–4.77) and anxiety (RR = 2.66, 95% CI: 1.27–5.55) in patients with rare cancers compared to healthy controls. The suicide incidence was 315 per 100,000 person-years, and the prevalence of depression, anxiety, and PTSD was 17%, 20%, and 18%, respectively. Compared to common cancer patients, rare cancer patients had higher rates of suicide and PTSD. Risk factors for negative psychological outcomes included advanced disease, chemotherapy treatment, lower income, and social status. The study highlights the need for early identification of psychological maladjustment in patients with rare cancers and emphasizes the importance of targeted interventions to address these challenges. The findings underscore the significant psychological burden faced by patients with rare cancers and the need for improved support and care strategies.This systematic review and meta-analysis evaluated the psychological outcomes of patients with rare cancers, including depression, anxiety, suicide, and post-traumatic stress disorder (PTSD), compared to healthy controls and common cancer patients. The study included 32 studies with 57,470 patients with rare cancers. The results showed a statistically significant increased risk of depression (RR = 2.61, 95% CI: 1.43–4.77) and anxiety (RR = 2.66, 95% CI: 1.27–5.55) in patients with rare cancers compared to healthy controls. The suicide incidence was 315 per 100,000 person-years, and the prevalence of depression, anxiety, and PTSD was 17%, 20%, and 18%, respectively. Compared to common cancer patients, rare cancer patients had higher rates of suicide and PTSD. Risk factors for negative psychological outcomes included advanced disease, chemotherapy treatment, lower income, and social status. The study highlights the need for early identification of psychological maladjustment in patients with rare cancers and emphasizes the importance of targeted interventions to address these challenges. The findings underscore the significant psychological burden faced by patients with rare cancers and the need for improved support and care strategies.