The extraction of uranium from seawater offers a sustainable pathway to secure nuclear fuel supplies, crucial for the transition to low-carbon energy systems. However, the low concentration of uranium and interference from competing ions pose significant challenges to extraction efficiency. Surface wettability engineering has become a key factor in enhancing the performance of nanomaterials. In this Perspective, we explore how surface wettability influences the performance of the nanomaterials in three uranium extraction scenarios: chemical adsorption, electro-assisted enhanced adsorption, and photo/electrocatalytic reduction. Strategies for optimizing this property are discussed, alongside recommendations and future directions in material design and characterization methods, aiming to accelerate the practical application of nanomaterials in seawater uranium extraction.