This paper summarizes the systematic regional investigation of underwater archaeology, and probes into the method, workflow and value connotation of the regional systematic investigation in underwater archaeology through the investigation of underwater cultural heritage resources in Yushan Islands. The research points out that the core of the systematic regional investigation method of underwater archaeology is its comprehensiveness and systematicness. Its working process can be divided into six steps as follows: comprehensively and systematically combing background information-screening key underwater investigation areas-looking for doubts about underwater remains-investigation and confirmation of underwater remainsinformation collection of underwater remains-information collection of underwater remains. At present, there are still great challenges in the systematic regional survey method of underwater archaeology. In addition to the ununified survey standards and the lack of applied research, the technology of marine geophysical exploration needs to be improved. Underwater visibility, water depth and other factors also affect the efficiency of underwater exploration. It is difficult to confirm the underwater suspected target of deep burial or in complex environment. It is suggested that we should strengthen the application research of regional survey methods of underwater archaeology, actively introduce new technological means and equipment, focus on interdisciplinary cooperation and international cooperation and exchange, and constantly enrich and improve the methodological system of regional systematic investigation.