Yaws and malaria are both significant health burdens in the Pacific today. However, the timing and route of their introduction into the Pacific is largely unknown. There is strong evidence for both diseases having roots in deep antiquity in Mainland Southeast Asia. Thalassaemia, a genetic anaemia with close evolutionary ties to endemic malaria, has been identified in hunter-gather communities in northern Vietnam from almost 7000 years ago. Yaws has similarly been present from at least 4000 years ago with the emergence of agriculture in the region. Earliest evidence in the Pacific for yaws, however, is only about 1200 years old, and no clear evidence for early malaria has yet been discovered in any of the islands. The dearth of evidence of malaria is largely because indirect skeletal evidence of sequelae or genetic anaemia is the only way to identify malaria in archaeological skeletal assemblages. We explore the potential pathways these pathogens may have taken to be introduced into the Pacific, and propose regions of future investigation, as well as new technologies to solve the problems our field has faced in answering questions of malarial and yaws disease burdens in human populations in the past. We argue that we now have the resources to answer these questions that have eluded researchers in the Indo-Pacific region of the world for decades.