Cancer is a significant problem for the South Pacific region due to a range of complex health challenges. Currently gaps in diagnosis, treatment and palliative care are significant, and while governmental commitment is strong, economic constrains limit health system strengthening. Alliances have been successful in strengthening non-communicable disease and cancer control policy and services in resource constrained settings. A regional coalition approach has therefore been recommended as an effective solution to addressing many of the challenges for cancer control in the South Pacific. However, evidence regarding the effective mechanisms for development of alliances or coalitions is scarce. This study aimed to 1) create a Coalition Development Framework; 2) assess the use of the Framework in practice to co-design a South Pacific Coalition. Creation of the Coalition Development Framework commenced with a scoping review and content analysis of existing literature. Synthesis of key elements formed an evidence-informed step-by-step guide for coalition-building. Application of the Framework comprised consultation and iterative discussions with key South Pacific cancer control stakeholders in Fiji, New Caledonia, Papua New Guinea, Samoa and Tonga. Concurrent evaluation of the Framework utilising Theory of Change (ToC) and qualitative analysis of stakeholder consultations was undertaken. The finalised Coalition Development Framework comprised four phases with associated actions and deliverables: engagement, discovery, unification, action and monitoring. Application of the Framework in the South Pacific identified overwhelming support for a Cancer Control Coalition through 35 stakeholder consultations. Framework phases enabled stakeholders to confirm coalition design and purpose, strategic imperatives, structure, local foundations, barriers and facilitators, and priorities for action. ToC and thematic consultation analysis confirmed the Framework to be an effective mechanism to drive engagement, unification and action in alliance-building. A Coalition to drive cancer control has significant support among key Pacific stakeholders, and establishment can now be commenced. Importantly results confirm the effective application of the Coalition Development Framework in an applied setting. If momentum is continued, and a regional South Pacific Coalition established, the benefits in reducing the burden of cancer within the region will be substantial. This work was completed for a Masters of Public Health project. Cancer Council Australia provided project funding.