The proposed PROSPECTOMICS project intends to develop a radically new approach to Hydrocarbon (HC) prospecting based on molecular biological techniques. PROSPECTOMICS is the first project that utilizes the full potential of recent advances in so-called next-generation sequencing (NGS) with respect to hydrocarbon prospecting. Only the very recent developments in sequencing technology and the massive reduction in cost allow such a project to be carried out at an informative scale, which would have been unthinkable less than 10 years ago. PROSPECTOMICS brings together vastly different fields (Biogeochemistry, Metagenomics, Metatranscriptomics, Metaproteomics, Bioinformatics, Machine Learning) and uses their individual strengths to complement each other in order to develop a completely novel approach that has the potential to challenge current technical paradigms. The PROSPECTOMICS consortium consists of six groups from four countries, each an expert for one specific technology. Partnership with a petroleum exploration company guarantees a direct connection to real world conditions and uniquely offers the opportunities to immediately to field-test the hypotheses generated. Despite ongoing efforts to increase the percentage of renewable energy resources, HC will remain an important energy source for several decades. One of the key factors to reach EU’s ambitious goals in reduction of greenhouse gas emissions is the replacement of coal by other energy sources, mainly natural gas. Additionally, increasing global competition for resources and rising energy prices as well as price differentials between the European Union and its competitors requires energy which is sustainable, affordable and with a secure and reliable supply. Exploration for new resources within the EU are a key factor for reaching these goals. PROSPECTOMICS will help to meet these challenges by paving the way for completely novel approaches to HC prospecting.