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Pain continues to be a significant problem for cancer patients, and the impact of a population-based strategy on their experiences is not completely understood. Our study aimed to determine the impact of palliative care on mitigating pain and its associated effects in determining the quality of life (QoL) among colon cancer outpatients. Six collection databases were used to perform a structured systematic review of the available literature, considering all papers published between the year 2000 and February 2023. PRISMA guidelines were adopted in our study, and a total of 9792 papers were evaluated. However, only 126 articles met the inclusion criteria. A precise diagnosis of disruptive colorectal cancer (CRC) pain disorders among patients under palliative care is necessary to mitigate it and its associated effects, enhance health, promote life expectancy, increase therapeutic responsiveness, and decrease comorbidity complications. Physical activities, the use of validated pain assessment tools, remote outpatient education and monitoring, chemotherapeutic pain reduction strategies, music and massage therapies, and bridging social isolation gaps are essential in enhancing QoL. We recommend and place a strong emphasis on the adoption of online training/or coaching programs and the integration of formal and informal palliative care systems for maximum QoL benefits among CRC outpatients.