Respiratory Syncytial Virus (RSV) is an enveloped RNA virus that causes severe lower respiratory tract infections in all age groups. It is the main cause of hospitalization during infancy and in adults, RSV is less studied but started to be recognized as an important pathogen, especially among elderly living with comorbidities. While RSV imposes a huge disease burden on the public healthcare system, the existing effective treatment options are limited. The development of RSV specific antivirals is partially impeded by a lack of knowledge of virus-host interactions and molecular mechanisms underlaying virus multiplication and pathogenicity. Here we present preliminary data on an integrated multi-omics approach that includes a RSV-host interaction network and the cellular response to RSV infection. By using state-of-the-art-of proteomics and transcriptomics, we characterized the RSV interactome, analyzed the proteome of cells expressing the individual viral proteins (effectome), and assessed the influence of RSV infection on cellular mRNA expression, protein abundance, and phosphorylation. The impact of some top candidates on viral replication dynamics was assessed by using a CRISPR/Cas9-based loss-of-function approach and time-course viral replication analysis of a GFP expressing recombinant RSV. Overall, the proposed approach will thus reveal yet unstudied proteins and pathways determining RSV growth, viral host defense mechanisms or disease severity, which will shed light on unresolved questions of RSV biology and reveal hotspots amenable to therapeutic intervention.