Background: Despite advances in cancer diagnosis and treatment have significantly improved survival rates, patients post-treatment-related health needs are often not adequately addressed by current health services. The aim of the Women's Wellness after Cancer Program (WWACP), which is a digitised multimodal lifestyle intervention, is to enhance health-related quality of life in women previously treated for blood, breast and gynaecological cancers. Methods: A single-blinded, multi-centre randomized controlled trial recruited a total of 330 women within 24 months of completion of chemotherapy (primary or adjuvant) and/or radiotherapy. Women were randomly assigned to either usual care or intervention using computer-generated permuted-block randomisation. The intervention comprises an evidence-based interactive iBook and journal, web interface, and virtual health consultations by an experienced cancer nurse trained in the delivery of the WWACP. The 12 week intervention focuses on evidence-based health education and health promotion after a cancer diagnosis. Components are drawn from the American Cancer Research Institute and the World Cancer Research Fund Guidelines (2010), incorporating promotion of physical activity, good diet, smoking cessation, reduction of alcohol intake, plus strategies for sleep and stress management. The program is based on Bandura's social cognitive theoretical framework. The primary outcome is health-related quality of life, as measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Secondary outcomes are menopausal symptoms as assessed by Greene Climacteric Scale; physical activity elicited with the Physical Activity Questionnaire Short Form (IPAQ-SF); sleep measured by the Pittsburgh Sleep Quality Index; habitual dietary intake monitored with the Food Frequency Questionnaire (FFQ); alcohol intake and tobacco use measured by the Australian Health Survey and anthropometric measures including height, weight and waist-to-hip ratio. All participants were assessed with these measures at baseline (at the start of the intervention), 12 weeks (at completion of the intervention), and 24 months (to determine the level of sustained behaviour change). Further, a simultaneous cost-effectiveness evaluation will consider if the WWACP provides value for money and will be reported separately. Discussion: Women treated for blood, breast and gynaecological cancers demonstrate increasingly good survival rates. However, they experience residual health problems that are potentially modifiable through behavioural lifestyle interventions such as the WWACP.