Colon cancer (RC) patients holding an intestinal stoma recorded lower health-related quality of life (HRQOL) levels. Intestinal stoma leads to several difficulties, like travel, work, and sporting activities. Patients with an intestinal stoma frequently experienced changes in their HRQOL. The COH-QOL-Ostomy questionnaire comprehensively measured these changes across physical, psychological, social, and spiritual domains. We reviewed literature in order to assess any differences in HRQOL between females and males and between intestinal stoma permanence among these patients. We conducted a literature review from: British Nursing Collection, Embase, MEDLINE, Nursing & Allied Health Database, PubMed, Scopus and Web of Science databases, without any time limits. The protocol was registered with PROSPERO no. CRD420251040414. A total of 492 records were identified. Of these, 362 records were removed, obtaining 130 potential records. However, 126 of these were excluded as they did not meet the inclusion criteria including only 4 records for further analysis. The COH-QOL-Ostomy questionnaire has been considered to assess HRQOL total score and its related sub dimensions, specifically physical, psychological, social and spiritual well-being. For each item, a Likert scale has been associated raging from zero (worse outcome) to 10 (good outcome). A total of 915 observations were collected, specifically 401 related to females and 514 to males. Additionally, a total of 670 observations were recorded: 338 belonging to the temporary group and 332 to the permanent one. Data reported a significant difference in the Psychological Well Being dimensions between the two groups, in favour of the female group (t = −3.66; p = 0.035). Considering the ostomy permanence, the temporary group reported a significant and better total quality of life score (t = −7.53; p = 0.017), Psychological Well Being dimension (t = −5.24; p = 0.035), and in social dimension (t = −8.09; p = 0.015), too. Sex-related differences in HRQOL assessments could help patients to achieve the most appropriate interventions to ameliorate QOL perceptions. Permanence criteria for ostomy could better address healthcare professionals for a specific clinical pathway to improve, especially in social support, which could positively contribute to better self-care for these patients.