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Abstract During recent years, several companies have introduced small autonomous delivery robots and evidenced their technical applicability in field studies. However, a holistic planning framework for routing and utilizing these robots is still lacking. Current literature focuses mainly on logistical performance of delivery using autonomous robots, ignoring real world limitations, and does not assess the respective impact on total delivery costs. In contrast, this paper presents an approach to cost‐optimal routing of a truck‐and‐robot system for last‐mile deliveries with time windows, showing how to minimize the total costs of a delivery tour for a given number of available robots. Our solution algorithm is based on a combination of a neighborhood search with cost‐specific priority rules and search operators for the truck routing, while we provide and evaluate two alternatives to solve the robot scheduling subproblem: an exact and a heuristic approach. We show in numerical experiments that our approach is able to reduce last‐mile delivery costs significantly. Within a case study, the truck‐and‐robot concept reduces last‐mile costs by up to 68% compared to truck‐only delivery. Finally, we apply sensitivity analyses to provide managerial guidance on when truck‐and‐robot deliveries can efficiently be used in the delivery industry.