The past few years observed a breakthrough of genome sequences of bacteria of Rhodococcus genus with significant biodegradation abilities. Invaluable knowledge from genome data and their functional analysis can be applied to develop and design strategies for attenuating damages caused by hydrocarbon contamination. With the advent of high-throughput -omic technologies, it is currently possible to utilize the functional properties of diverse catabolic genes, analyze an entire system at the level of molecule (DNA, RNA, protein, and metabolite), simultaneously predict and construct catabolic degradation pathways. In this review, the genes involved in the biodegradation of hydrocarbons and several emerging plasticizer compounds in Rhodococcus strains are described in detail (aliphatic, aromatics, PAH, phthalate, polyethylene, and polyisoprene). The metabolic biodegradation networks predicted from omics-derived data along with the catabolic enzymes exploited in diverse biotechnological and bioremediation applications are characterized.