Nowadays, soil contamination by total petroleum hydrocarbons is still one of the most widespread forms of contamination. Intervention technologies are consolidated; however, full-scale interventions turn out to be not sustainable. Sustainability is essential not only in terms of costs, but also in terms of restoration of the soil resilience. Bioremediation has the possibility to fill the gap of sustainability with proper knowledge. Bioremediation should be optimized by the exploitation of the recent “omic” approaches to the study of hydrocarburoclastic microbiomes. To reach the goal, an extensive and deep knowledge in the study of bacterial and fungal degradative pathways, their interactions within microbiomes and of microbiomes with the soil matrix has to be gained. “Omic” approaches permits to study both the culturable and the unculturable soil microbial communities active in degradation processes, offering the instruments to identify the key organisms responsible for soil contaminant depletion and restoration of soil resilience. Tools for the investigation of both microbial communities, their degradation pathways and their interaction, will be discussed, describing the dedicated genomic and metagenomic approaches, as well as the interpretative tools of the deriving data, that are exploitable for both optimizing bio-based approaches for the treatment of total petroleum hydrocarbon contaminated soils and for the correct scaling up of the technologies at the industrial scale.