Cyber defense requires automating defensive decision-making under stealthy, deceptive, and continuously evolving adversarial strategies. The FlipIt game provides a foundational framework for modeling interactions between a defender and an advanced adversary that compromises a system without being immediately detected. In FlipIt, the attacker and defender compete to control a shared resource by performing a Flip action and paying a cost. However, the existing FlipIt frameworks rely on a small number of heuristics or specialized learning techniques, which can lead to brittleness and the inability to adapt to new attacks. To address these limitations, we introduce PoolFlip, a multi-agent gym environment that extends the FlipIt game to allow efficient learning for attackers and defenders. Furthermore, we propose Flip-PSRO, a multi-agent reinforcement learning (MARL) approach that leverages population-based training to train defender agents equipped to generalize against a range of unknown, potentially adaptive opponents. Our empirical results suggest that Flip-PSRO defenders are $2\times$ more effective than baselines to generalize to a heuristic attack not exposed in training. In addition, our newly designed ownership-based utility functions ensure that Flip-PSRO defenders maintain a high level of control while optimizing performance.