This thesis summarizes contributions to the solution of decision-making problems that arise in transportation systems. It focuses on operations research techniques with an emphasis on mixed-integer programming based approaches. These contributions have been organized into three main chapters that differ by the methods used therein, as well as by the decision-making problems selected. One chapter is dedicated to bilevel optimization and its application to transportation network design problems. The next chapter turns to mixed-integer nonlinear programming and its application to aircraft conflict resolution problems. The remaining chapter embraces a broader modeling perspective by summarizing different approaches from mathematical programming to mechanism design for autonomous intersection management. Throughout this thesis, both theoretical and numerical results are reported, and perspectives are discussed to outline future research directions in optimization and game-theoretical methods for transportation systems