The promotion of the development of co-digestion power plants will be intensified in many European Union member states as the main target of the Union concerning energy generation is complete decarbonisation by 2050. This potential expansion prompts the need for optimal resources allocation according to several techno-economical parameters, highlighting energy costs, power infrastructures access, and social and environmental aspects and restrictions. In Spain, agricultural and livestock biogas production trough co-digestion power plants is still poorly deployed, although the EU Directive 2009/28/EU stipulates that energy from bio-fuels and bio-liquids should contribute to a reduction of at least 35% of greenhouse gas emissions in order to be taken into account, and many authors agree that biogas produced from energy crops and livestock waste fulfils this criterion. Moreover, biogas can be used to upgrade gas pipelines and may have other efficient thermal uses. In this paper, through a Geographical Information System approach, eight different co-digestion mixtures have been evaluated and the most profitable ones have been optimized for the Spanish Iberian Peninsula according to the geographical distribution of the resources. Furthermore, the best locations for co-digestion power plants siting have been calculated, minimizing transport costs and considering technical, environmental and social restrictions. In contrast with other studies, this proposed approach is focused on a holistic optimization. Results show that in Spain the most feasible co-digestion mixtures are based on slurry, glycerine and animal meals, and four areas arise with an outstanding energetic potential up to 208 MW exploitable in large electrical power plants, while 347 MW can be reserved for distributed generation based on this technology.