With an increase in international projects, comes increased opportunities for design researchers to contribute to research that tackles Sustainable Development Goals in the Global South. Nevertheless, the role of design within this context is disparate and detached, with very limited design literature on the subject. As such, this paper has identified the key challenges and barriers that design researchers face in conducting and applying design research in a Global South Context. Based on a workshop with design research experts doing research in Global South, the literature and lessons learnt from running a design-led project in Ghana, we are presenting and discussing 45 challenges grouped under 13 themes. We envisage that these will form the first step towards developing strategies for mitigating these challenges and help current and future design researchers to engage further in international research in the Global South.