Late-onset Pompe Disease (LOPD) is a subtype of Pompe Disease (PD) that manifests any time after infancy. This review explores the efficacy, safety and limitations of various therapeutic options for LOPD, including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), pharmacological chaperone therapy (PCT), supplementary therapies, and gene therapy from inception to February 2025, and compares them where possible. Emphasis is given to therapeutic selection and the potential for switching between approved ERT formulations based on the recently updated Triple-S (Start, Switch, Stop) consensus recommendations. A literature search was done on PubMed, ScienceDirect, and Embase utilizing MESH terms, keywords, and Boolean operators. It included all English-language studies relevant to our topic from inception to February 2025. Among the ERT, alglucosidase alfa significantly improves the 6-min walk test (6MWT) and forced vital capacity (FVC%), but immunogenic and infusion-related reaction rates are high. On the contrary, avaglucosidase alfa has superior efficacy in improving 6MWT and FVC% along with fewer side effects. Cipaglucosidase alfa +miglustat, which is an approved alternative ERT rather than an adjunctive or emerging therapy, shows favorable motor and respiratory outcomes compared with standard ERT but they are associated with a much higher incidence of side effects. Moreover, adding clenbuterol to ERT might improve motor and respiratory function, but it is associated with cardiovascular risks. PCT, SRT, and Gene Therapy show mild motor and respiratory improvement, but due to limited studies, their efficacy and safety are still uncertain. Conclusion: Three approved ERT options—alglucosidase alfa, avaglucosidase alfa, and cipaglucosidase alfa+ miglustat—are now available for LOPD management and should be considered therapeutic alternatives rather than adjunctive or emerging treatments. Avaglucosidase alfa remains the most effective treatment option with fewer adverse effects. Based on the Triple-S consensus, switching between ERTs should be considered in cases of suboptimal response, intolerance, or significant adverse events, to ensure individualized and optimized patient care. Also, cipaglucos