This book constitutes the refereed proceedings of the 6th IFIP TC 5, TC 12, WG 8.4, WG 8.9, WG 12.9 International Cross-Domain Conference, CD-MAKE 2022, held in Vienna, Austria during August 2022.The 23 full papers presented were carefully reviewed and selected from 45 submissions. The papers are covering a wide range from integrative machine learning approach, considering the importance of data science and visualization for the algorithmic pipeline with a strong emphasis on privacy, data protection, safety and security.