Transcriptome analysis technologies are important systems-biology methods for the investigation and optimization of mammalian cell cultures concerning with regard to growth rates and productivity. For the production of recombinant proteins, knowledge of the expression conditions of the influencing genes is a major issue in the improvement of cell lines by means of genome engineering. This chapter presents two main techniques for transcriptome analysis: microarray technology and next-generation sequencing. Protein-based methods are also briefly outlined. Furthermore, the impact of these technologies on mammalian cell culture improvement is discussed.