Drug repurposing, identifying FDA-approved drugs for new indications, reduces the time and money required for a drug to reach the clinic and capitalizes on the increasing number of publicly available online data. Attrition rates for repurposing studies are lower than compared to drug discovery. Still, repurposing candidates often fail downstream despite their biological relevance, attributing to a lack of safety and/or efficacy. Current approaches may be limited in separating biological signals from technical noise and incorporating relevant clinical information to evaluate promising candidates in preclinical analyses. Many drug repurposing approaches have been developed; however, a gold standard has yet to be determined. In addition, repurposing analyses often yield many potential candidates that require further prioritization to ensure clinical viability. Thus, prioritization of the optimal candidates by incorporating more information from available resources is critical. Here, we reviewed prioritization criteria and developed a workflow implementing 1) drug-specific, 2) target-specific, and 3) disease-specific considerations to address challenges in current drug repurposing efforts. Our workflow streamlines drug candidate prioritization using a stepwise evaluation process and vetted resources for each consideration to guide researchers in better predicting the most robust candidates and facilitating the most promising ones for clinical adoption.