Many packing, routing, and knapsack problems can be expressed in terms of integer linear programming models based on set covering. These models have been exploited in a range of successful heuristics and exact techniques for tackling such problems. In this paper, we show that integer linear programming models based on set covering can be very useful for their use within an algorithm called “Construct, Merge, Solve & Adapt”(CMSA), which is a recent hybrid metaheuristic for solving combinatorial optimization problems. This is because most existing applications of CMSA are characterized by the use of an integer programming solver for solving reduced problem instances at each iteration. We present applications of CMSA to the variable-sized bin packing problem and to the electric vehicle routing problem with time windows and simultaneous pickups and deliveries. In both applications, CMSA based on a set covering model strongly outperforms CMSA when using an assignment-type model. Moreover, state-of-the-art results are obtained for both considered optimization problems.