Abstract: A large amount of waste has been produced in the intensive livestock industry in recent years. A series of threats can be found in the natural ecological system. The end treatment is essential to promote the sustainable development of animal husbandry, particularly for the pollutant reduction, resource valorization, and harmless treatment of livestock waste. The biogas project has been the most economical and effective mode to convert the organic matter of manure into the renewable energy. There are over 100 thousand biogas projects in different scales in China nowadays. A great contribution has been made to promote the resource recovery efficiency for the reduction of the fecal loss, malodorous gas escape, and greenhouse gas production. Nevertheless, the complicated system has posed a great challenge on to the construction, operation, and management of biogas projects for the livestock manure in recent years. It is necessary to fully realize the systematical technology via the engineering management in the biogas industry. The innovative third-party operation mode has been introduced to the large-scale biogas project at present. The management strategy has been also utilized to fully realize the eco-friendly and high-efficient manure treatment. Therefore, it is necessary to explore the resource valorization and benefit evaluation of manure treatment projects in large-scale farms. In this study, the third-party operation of the biogas project was proposed to carry out the multi-perspective analysis of material flow, energy flow, environmental and economic evaluation. A case study was taken as the cow manure biogas plant (total available fermentation volume 10 800 m³) over the a 20-year period. Besides, an optimization strategy of the fermentation process was provided to analyze the biogas output using gene expression programming. The results show that the third-party operation was improved both engineering efficiency and economic benefits. The handling capacity of biogas projects, biogas output, and biogas power generation under the third-party operating mode increased by 52.00%, 23.00%, and 79.58%, respectively, compared with the self-operation mode. The total capacity of cogeneration is improved under the third-party operation. However, the energy consumption ratio and the energy recovery rate reduced by 14.74% and 12.73% respectively, which was mainly caused by the lack of waste heat recovery. The financial analysis showed that the financial internal rate of return in the third-party operation mode increased by 10.20 percentage points, while the after-tax financial net present value increased by 35.66 million CNY, and the payback period was shortened by 10.42 years. In addition, the financial sensitivity analysis demonstrated that the ever-increasing added value of downstream products (biogas, slurry, and residue) was the key factor to improve the economic benefits of the biogas project. And, the carbon emission reduction was 77.71% higher under the third-party operation mode than that under the self-operation one, indicating more positive environmental benefits. This finding can provide an engineering reference and process optimization strategy for the popularization of third-party operation mode in large-scale biogas projects and waste treatments.