Objectives. To examine public health nurse (PHN) intervention tailoring through the Colorado Nurse Support Program (NSP). Our 2 specific aims were to describe the NSP program and its outcomes and to determine the effects of modifying interventions on short- and long-term outcomes among NSP clients. Methods. In our retrospective causal investigation of 150 families in Colorado in 2018-2019, intervention effects were modeled via longitudinal modified treatment policy analyses. Results. Families served by PHNs improved in terms of knowledge, behavior, and status outcomes after receiving multidimensional, tailored home visiting interventions. Case management interventions provided in the first month of PHN home visits had lasting effects on behavior outcomes, and 2 additional case management interventions in the first month were estimated to have even more of an impact. Conclusions. Modern causal inference methods and real-world PHN data revealed a nuanced, fine-grained understanding of the real impact of tailored PHN interventions. Public Health Implications PHN programs such as the NSP and use of the Omaha System should be supported and extended to advance evaluations of intervention effectiveness and knowledge discovery and improve population health. (Am J Public Health. 2022;112(S3):S306-S313. https://doi.org/10.2105/AJPH.2022.306792).