Background: The first five years post-treatment for breast cancer are a critical phase, when the survivors may face a multitude of physical and psychosocial problems. We aimed to develop an e-home based symptom management and mindfulness training program to support women with breast cancer in transition to survivorship and to determine its effect on the endpoints including quality of life, symptom distress, psychosocial adjustment, and psychological morbidity. Methods: This parallel 4-arm, superiority randomized clinical trial together with a process evaluation using semi-structured interview recruited women who had completed cancer treatment for stage 0 to 3 breast cancer between 6 months to 5 years previously, from November 2016 through March 2020 at two tertiary hospitals. A total of 593 women were eligible, of these, 402 refused to participate and 191 women were randomized. However, 19 subjects withdrew from the study without completion of baseline assessments. Hence, 172 subjects were included in the intention-to-treat analysis (e-home based breast cancer survivorship program, experimental group; n = 44), comparison group 1 (online symptom management program only; n = 41), comparison group 2 (online mindfulness training program only; n = 44) or the usual care group (n = 43). The e-home based breast cancer survivorship program involved 5 weekly online education module regarding self-management strategies of common symptoms + various online self-administered mindfulness exercises. The primary endpoint included change of Quality of Life-Cancer Survivor Scale (QoL-CS) score measured at 8, 12 and 24 weeks from baseline. Secondary endpoints were changes of Social Support Questionnaire, Breast Cancer Survivor Self-Efficacy Scale, Memorial Symptom Assessment Scale, Psychosocial Adjustment to Illness Scale, Fear of Recurrence Scale, Hospital and anxiety Depression Scale, and Five Facet Mindfulness Questionnaire scores. Results: Of 172 subjects, mean ± SD age was 51.2 ± 9.4 years; 118 (77.7%) were in the first two years of cancer treatment completion; 165 (98.2%) underwent surgery; and 111 (73.5%) treated with adjuvant chemotherapy. All demographic and clinical characteristics were comparable among the four groups (p>.05). There was no between-group difference in the primary endpoint; QoL-CS scores among groups at 8, 12 and 24 weeks from baseline (p>.05). Secondary endpoints were also not different among groups (p>.05). Two main themes; positive impact and gap/barrier, emerged from process evaluation data. Conclusions: In women who were in the first five years post-breast cancer treatment, an e-home based multidimensional cancer survivorship program did not affect outcomes. Nevertheless, the interview data revealed a positive experience in regards to the home-based approach in cancer survivorship care program. Clinical trial information: NCT02931864