In recent years, with the rapid development of cross-border e-commerce and the transformation and upgrading of traditional foreign trade of various countries, both China and ASEAN regard cross-border e-commerce as an important content to promote the high-quality development of bilateral trade. The Guangdong-Hong Kong-Macao Greater Bay Area is a key global trade digital pilot area. The official entry into force of the RCEP provides a new environment for the development of cross-border e-commerce between the Greater Bay Area and ASEAN countries. From the background of RCEP framework, this paper analyzes the opportunities and challenges faced by cross-border e-commerce enterprises in the Greater Bay Area and ASEAN. Based on this, it proposes the innovative development path of cross-border e-commerce from the aspects of cross-border logistics system building, cross-border e-commerce talent team building and cross-border e-commerce intellectual property protection. It is aimed to activate the Greater Bay Area commodity trade market, and further promote the development of cross-border e-commerce between the Greater Bay Area and ASEAN countries.