A spacecraft tour trajectory is a trajectory in which a spacecraft visits a number of objects in sequence. The target objects may consist of satellites, moons, planets or any other body in orbit, and the spacecraft may visit these in a variety of ways, for example flying by or rendezvousing with them. The key characteristic is the target object sequence which can be represented as a discrete set of decisions that must be made along the trajectory. When this sequence is free to be chosen, the result is a hybrid discrete-continuous optimization problem that combines the challenges of discrete and combinatorial optimization with continuous optimization. The problem can be viewed as a generalization of the traveling salesman problem; such problems are NP-hard and their computational complexity grows exponentially with the problem size. The focus of this dissertation is the development of a novel methodology for the solution of spacecraft tour trajectory optimization problems. A general model for spacecraft tour trajectories is first developed which defines the parameterization and decision variables for use in the rest of the work. A global search methodology based on the tabu search metaheuristic is then developed. The tabu search approach is extended to operate on a tree-based solution representation and neighborhood structure, which is shown to be especially efficient for problems with expensive solution evaluations. Concepts of tabu search including recency-based tabu memory and strategic intensification and diversification are then applied to ensure a diverse exploration of the search space. The result is an automated, adaptive and efficient search algorithm for spacecraft tour trajectory optimization problems. The algorithm is deterministic, and results in a diverse population of feasible solutions upon termination. A novel numerical search space pruning approach is then developed, based on computing upper bounds to the reachable domain of the spacecraft, to accelerate the search. Finally, the overall methodology is applied to the fourth annual Global Trajectory Optimization Competition (GTOC4), resulting in previously unknown solutions to the problem, including one exceeding the best known in the literature. / text