Mammalian cells, particularly Chinese hamster ovary (CHO) cells, have been predominantly used for the production of high-value bio-therapeutics such as monoclonal antibodies, recombinant proteins and viral vaccines. The increasing market demand for such commercially valuable compounds can be satisfied by developing high-yielding mammalian cell culture processes based on a good understanding of the cellular response of the production host. However, it is challenging to elucidate these cellular responses as the mammalian cellular system is structurally, functionally and dynamically intricate. Recent advances in various “-omics” platforms have resulted in rapid accumulation of biological data at the genome, transcriptome, proteome and metabolome levels, which allows us to tackle such a challenge. BTI has harnessed these technologies towards the understanding and engineering of CHO cell lines and culture processes. This talk highlights some of these examples, including the use of targets identified from transcriptomic and proteomic data to generate apoptosis-resistant Gene-Targeted (GT) CHO cell lines; and the use of metabolomics to identify growth-limiting nutrients in high-density fed-batch processes. More recently, we have started to establish more systematic strategies for managing and analyzing heterogeneous “-omics” data under an integrated bioinformatics platform. This will lead to advanced mining and integration of the vast amount of data generated, thereby developing more global approaches for the characterization and improvement of CHO cell lines and culture processes. Future perspectives on “systems bioinformatics” in mammalian cell cultures are also discussed to suggest new opportunities and challenges in this field.