Cognitive abilities and interests both play an important role in guiding knowledge acquisition, but most previous studies have examined them separately. The current study used a large and representative dataset to integrate interests and abilities using a person-centered approach that examines how distinct profiles of interests and abilities relate to individual strengths and weaknesses in knowledge. Two key findings emerged. First, eight interest-ability profiles were generated from Latent Profile Analysis (LPA), which replicated and extended the interrelations of interests and abilities found in previous studies using variable-centered approaches. Second, each profile's strongest knowledge scores corresponded to their strongest abilities and interests, highlighting the importance of interest-ability profiles for guiding the development of knowledge. Importantly, in some domains, the lower ability profiles were actually more knowledgeable than higher ability profiles. Overall, these findings suggest that people learn best when given opportunities to acquire knowledge relevant to both their interests and abilities. We discuss how interest--ability profiles inform integrative theories of psychological development and present implications for education and career development.