Rare diseases represent a significant challenge for biomedical research due to limited data availability and complex molecular interactions. Multi-omics integration emerges as a promising strategy to overcome individual omics limitations and provide comprehensive biological insights. This work presents a comparative analysis of multi-omics integration approaches applied to Ehlers-Danlos Syndrome (EDS), a group of hereditary rare diseases characterized by collagen production defects. The research operates on three analytical levels: first, single omics analysis, performed on transcriptomics and proteomic data, followed by multiomics integration through statistical techniques. All the levels of analysis are performed on bulk (2D) and spheroid cell (3D) cultures, to capture shared information and compare possible differences.