Cooperation between Zhuhai and Macao in technological innovation plays an important role to support the Guangdong-Hong Kong-Macao Greater Bay Area to build an international technological innovation center. Through examining the status quo of Zhuhai-Macao cooperation in technological innovation，some challenges and problems have been found such as unclear orientation of cooperation，imperfect mechanism for coordinated development，insufficient reserve of resources，lack of motivation，interrupted flow of innovation factors，weak agglomeration effect of international resources. On this basis，the paper gives some suggestions in six aspects：cooperation mechanisms，multi-level linkage between departments，innovation ecology optimization，transformation of scientific and technological achievements，global strategy，and breaking through the barriers of factor flow.