Infectious animal diseases can cause severe mortality on infected farms. An outbreak challenges the system and forces difficult decisions to stop the disease progression. We propose an ‘all-in-one’ concept of a mobile system for on-farm swine depopulation and pathogen inactivation. The system uses vaporized CO2 followed by heat treatment, broadening options for off-site carcass disposal and cleanup. A direct-fired heater supplies heat into the insulated trailer to reach and maintain the inactivation temperature for targeted pathogens. We developed a user-friendly model based on engineering principles for estimating site- and scenario-specific CO2 amounts and times required to inactivate targeted pathogens. Multipoint CO2 injection and improved distribution to animals follow the plug-flow reactor air replacement model. The model illustrates the depopulation and inactivation of two diseases, African swine fever (ASF) and the porcine reproductive and respiratory syndrome (PRRS) viruses. The model allows for dump trailer size, pig number, weights, and environmental conditions input. Model outputs provide users with practical information about the required CO2 injection rate, temperature setpoints, and times to effectively depopulate and inactivate pathogens in carcasses. The concept could be adopted for a routine or a mass depopulation/treatment/disposal with a single or fleet of ‘all-in-one’ units.