Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.