Background Precision public health (PPH) can maximize impact by targeting surveillance and interventions by temporal, spatial, and epidemiological characteristics. Although rapid diagnostic tests (RDTs) have enabled ubiquitous point-of-care testing in low-resource settings, their impact has been less than anticipated, owing in part to lack of features to streamline data capture and analysis. Objective We aimed to transform the RDT into a tool for PPH by defining information and data axioms and an information utilization index (IUI); identifying design features to maximize the IUI; and producing open guidelines (OGs) for modular RDT features that enable links with digital health tools to create an RDT-OG system. Methods We reviewed published papers and conducted a survey with experts or users of RDTs in the sectors of technology, manufacturing, and deployment to define features and axioms for information utilization. We developed an IUI, ranging from 0% to 100%, and calculated this index for 33 World Health Organization–prequalified RDTs. RDT-OG specifications were developed to maximize the IUI; the feasibility and specifications were assessed through developing malaria and COVID-19 RDTs based on OGs for use in Kenya and Indonesia. Results The survey respondents (n=33) included 16 researchers, 7 technologists, 3 manufacturers, 2 doctors or nurses, and 5 other users. They were most concerned about the proper use of RDTs (30/33, 91%), their interpretation (28/33, 85%), and reliability (26/33, 79%), and were confident that smartphone-based RDT readers could address some reliability concerns (28/33, 85%), and that readers were more important for complex or multiplex RDTs (33/33, 100%). The IUI of prequalified RDTs ranged from 13% to 75% (median 33%). In contrast, the IUI for an RDT-OG prototype was 91%. The RDT open guideline system that was developed was shown to be feasible by (1) creating a reference RDT-OG prototype; (2) implementing its features and capabilities on a smartphone RDT reader, cloud information system, and Fast Healthcare Interoperability Resources; and (3) analyzing the potential public health impact of RDT-OG integration with laboratory, surveillance, and vital statistics systems. Conclusions Policy makers and manufacturers can define, adopt, and synergize with RDT-OGs and digital health initiatives. The RDT-OG approach could enable real-time diagnostic and epidemiological monitoring with adaptive interventions to facilitate control or elimination of current and emerging diseases through PPH.