The means to achieve decarbonization of all economic sectors are an open question of difficult resolution. For example, remote communities and industrial or mining activities detached from the main electric grid heavily rely on fossil fuels, diesel fuel in particular, for heat and power production. A combination of renewables and energy storage is often unfeasible, due to the climate conditions and maintenance challenges typical of those locations. Urban and industrial micro-grids with combined heat and power also are often unsuitable for renewable energy source solutions due to their intermittency and large land requirements Until now fossil fuels have been the solution of choice. In a historic period in which carbon emissions were not of concern and fossil fuels were quite inexpensive and broadly available, the main advantage of nuclear power was limited to its independence from the need to transport and store high amounts of fuels onsite, with organizational, security, and economic benefits deriving from it. However, the nuclear industry has now a historic opportunity to bring the concept of very small reactors with a flexible purpose from the ideation phase to commercialization, and potentially transform the energy sector for decades to come. Modern materials and instrumentation and controls can support the development of compact and reliable plug-and-play nuclear reactors with low and predictable maintenance needs and very low probability of consequential accidents. Moreover, automated decision making enabling autonomous operation can help lower the need for human operators, thus reducing the cost of the energy products. These very small nuclear reactors are generally referred to as micro-reactors and have a thermal power output of less than 20 MW. To move further from the prototype to the commercialization phase, micro-reactors need a strong business case. In fact, fossil fuels are still relatively inexpensive and in the near-term carbon credits will continue to be available to virtually compensate for the emissions. Thus, the energy price at which micro-reactors will compete is uncertain and depends on the application, the location served, the fossil fuel costs and the carbon credits prices. One of the positive aspects of micro-reactors is that, compared to fossil fuel power generators, their fuel costs are a much smaller share of the total cost. Thus, once a reactor is built, the cost of the energy it produces tends to be more predictable and stable than with fossil fuel power generators. This can be a valuable feature for customers and investors, who can make more accurate predictions on the future economic viability of their energy assets. In this study, we have focused on operation and maintenance cost, and in particular on whether it is possible to optimize the number (and thus the cost) of two kinds of staff: maintenance workers and plant operators. In particular, we have investigated whether and how, with the aid of proper technologies, it is possible to reduce onsite staff while relying on a fleet-type centralized service business unit that shares the staff among multiple reactors and locations. This staff organization is completely different from current nuclear power plant operating experience and brings micro-reactors closer to the model of operation and maintenance of small aero-derivative gas turbines and similar small transportable 'plug-and-play' power units. In particular, we identify a reference staffing scenario, which represents the minimum staffing level that has to be present onsite to allow the micro-reactor to operate with limited offsite assistance and thus similarly to the current fleet of large nuclear power plants. Then, we identify the optimal staffing scenario, which should be the eventual goal for micro-reactors operation. In this case, no personnel are permanently onsite, the reactor operation is monitored remotely and maintenance workers go onsite only for programmed activities. We then describe the enabling technologies for this second scenario: autonomous operation, remote monitoring and predictive maintenance. We finally estimate the cost of the personnel and the technologies, and make cost comparisons. In this report, we show that the change in staff organization from onsite personnel to offsite personnel could translate to an annual cost saving of ~25% for these two operation and maintenance (O&M) invoices. We also argue that relying more on the use of technology for plant health monitoring will also mean a higher degree of safety. Ultimately, to move from a traditional fully-manned, onsite personnel approach to an unmanned, remote personnel approach, a robust operating experience and the approval from the regulator will be needed. It will be important to achieve a high level of confidence on the reliability of the installed technology and a solid understanding of possible malfunctions and failure modes that may arise. Finally, it will be important to achieve an appropriate confidence level among the population with regards to these new O&M approaches.