Sarcomas, neuroblastoma, and paediatric lung infections are difficult to treat, with little progress in developing new therapies over the past decades. Current treatments, such as chemotherapy, radiation, and surgery, have limited effectiveness, underscoring the need for new approaches. A deeper understanding of the tumour microenvironment (TME) and disease biology is crucial for advancing precision therapies. Our lab utilizes a combination of advanced multi-omics technologies to study the TME in paediatric sarcomas, neuroblastoma, and lung infections. These approaches provide deeper insights into cellular interactions and disease mechanisms, paving the way for more targeted and effective treatments. In this talk, I will discuss how multi-omics is driving innovation in treating these hard-to-cure paediatric diseases.