To gain a sustained competitive advantage, organizations such as UPS, Fedex, Amazon, etc., began to seek for industry 5.0 innovative autonomous delivery options for the last mile. Autonomous unmanned aerial vehicles are a promising alternative for the logistics industry. The fact that drones are propelled by green renewable energy source fits the companies’ need to become sustainable, replacing their fuel truck fleets, especially for traveling to remote rural locations to deliver small packages, but a major obstacle is the necessity for charging stations which is well documented in the literature. Therefore, the current research embarks on devising a novel yet practical piece of technology adopting the simplicity approach of direct flights to destinations. The analysis showcases the application for a network of warehouses and hospitals in Israel while controlling costs. Given the products in the case study are medical, direct flight has the potential to save lives when every moment counts. Hydrogen cell technology allows long-range flying without refueling, and it is both vibration-free which is essential for sensitive medical equipment and environmentally friendly in terms of air pollution and silence in urban areas. Importantly, hydrogen cells are lighter, with higher energy density than batteries, which makes them ideal for drone usage to reduce weight, maintain a longer life, and enable faster charging, all of which minimize downtime. Also, hydrogen sourcing is low-cost and unlimited compared to lithium-ion material which needs to be mined. The case study investigates an Israeli entrepreneurial company, Gadfin, which builds a vertical takeoff-and-landing-type of drone with folded wings that enable higher speed for the delivery of refrigerated medical cargo, blood, organs for transplant, and more to hospitals in partnership with the Israeli medical logistic conglomerate, SAREL. An analysis of shipping optimization (concerning the number and type of drone) is conducted using a mixed-integer linear programming technique based on various types of constraints such as traveling distance, parcel weight, the amount of flight controllers and daily number of flights allowed in order to not overcrowd the airspace. Importantly, the discussion assesses the ecosystem’s variety of risks and commensurate safety mechanisms for advancing a newly shaped landscape of drones in an Israeli tight airspace to establish a network of national routes for drone traffic. The conclusion of this research cautions limitations to overcome as the utilization of drones expand and offers future research avenues.