Among the Porifera, the taxonomy and systematics of Homoscleromorpha is one of the most challenging. Over the last two decades, this class and its single order Homosclerophorida have seen a high rate of new descriptions and phylogenetic investigations which have led to the resurrection of two well-supported families, defined as the ‘spiculate’ Plakinidae and the ‘aspiculate’ Oscarellidae. In recent years, the development of an integrative taxonomic approach and the exploration of new marine ecosystems have revealed an even higher diversity of Homoscleromorpha and highlighted the importance of complementary datasets (cytological, biochemical and molecular) to better explain the phylogenetic classification. Using this integrative approach, we here describe two new species of Plakinidae from submarine caves in the Caribbean Sea: Plakina arletensis sp. nov. and Aspiculophora madinina gen. nov. sp. nov., the latter being aspiculate with an unusually well-developed collagen layer in its mesohyl and an abundant and diverse prokaryote community. The recently described Oscarella nathaliae was reassigned to Plakina on the basis of new molecular data and a careful re-examination of morphological characters. Thus, Plakina nathaliae comb. nov. and A. madinina are the first aspiculate representatives of Plakinidae and indicate the need for a detailed re-examination of Homoscleromorpha using this integrative taxonomic approach.