The article proposes a modified Design-Based Research (DBR) framework which accommodates the various socio-cultural factors that emerged in the longitudinal PA-HELP research study at Central University College (CUC) in Ghana, Africa. A transnational team of stakeholders from Ghana, Canada, and the USA collaborated on the development, implementation, and subsequent modification of the DBR framework. The recommended framework is a result of lessons learned during this project in Ghana and as such, it is shaped by the need to be responsive to the local cultural and contextual contingencies. The article offers practical recommendations on the implementation of a mobile learning project in a cross-cultural setting, and provides a discussion of the salient cultural factors and the corresponding culturally-sensitive adaptations needed in the design research process. The Cross-Culture Design-Based Research (CC-DBR) framework is proposed to inform future transcultural m-learning studies.