The Virtual Factory Open Operating System (vf-OS) aims to become the reference system software for managing factory related computer hardware and software resources and providing common services for factory computational programs. Additionally, it provides a methodology to support the implementation of virtual factory applications to be deployed in industrial scenarios. This paper focuses on this proposed methodology that guides the virtual factory applications definition, development, and validation. It takes into account the industrial application requirements and specifications to technically and business validate its integration in the proposed vf-OS environment and in the real factory production. Thus, this methodology presents the successive steps and interactions that occur in the process, during the following proposed three phases. In the starting phase, the functionality of the application taking into consideration the actors involved in the process e.g. manufacturing and logistics users and software developers is defined. The development and test phase represent the moment in which the applications are developed, deployed and tested inside pilots’ premises. The evaluation phase is when applications are validated by the evaluators to guarantee that they fulfil the needs of the users. In line with these phases, the methodology presents templates and guidelines that both developers and users should fill to create a common understanding of what is desired. This includes a use case definition template, an application questionnaire, and guidelines for the creation of sketches, mock-ups, and workflow diagrams. This paper demonstrates the proposed methodology reporting the evaluation conducted in three different industrial pilots: 1) manufacturing and logistics or automation: applications focused on providing support to maintenance and spare part stock management in automation production equipment; 2) construction or industrialization: applications to improve time and resource utilization in construction projects through advanced collaboration between construction managers and material providers; 3) manufacturing assembly or collaboration: applications to enable collaborative design and manufacturing of complex products.