Since 2014, successive sanctions and counter-sanctions have defined the Russia-US-EU relationship, intensifying after the 2022 invasion of Ukraine. This chapter asks how strategic interdependence among these three actors shapes sanction effectiveness. An evolutionary game-theory framework models Russia (sanctionee), the US (lead sanctioner), and the EU (co-sanctioner), capturing shifting alliances, coordination frictions, and adaptive behavior. Simulations reveal a feedback loop: strong US measures trigger robust Russian retaliation, while internal distributional costs press the EU toward milder positions, fragmenting the coalition. The EU thus becomes the structural “weak link,” especially when energy trade and domestic politics raise its adjustment costs. Persistent Russian counter-sanctions barely deter Washington but amplify stress on Europe, eroding the combined coercive power. Policy lessons follow. Effective sanctions require clearly aligned US-EU strategies that reflect each side’s political and economic limits. Reducing Russia’s capacity to retaliate—through diversified energy sources or financial insulation—can prolong pressure. Yet broad sectoral sanctions inflict collateral harm on civilians. Policymakers should weigh these trade-offs and pursue cooperative dispute-resolution channels to minimize long-term economic and diplomatic damage.