Exosomes are extracellular vesicles that facilitate communication among cells by exchanging signaling biomolecules with adjacent cells. Among the diverse signaling biomolecules, long noncoding RNAs (lncRNAs) can be selectively packaged into exosomes to influence cancer onset and progression through various mechanisms. This study aimed to explore the role of exosomal lncRNA SCAMP1-AS1 in osteosarcoma (OS). The expression of SCAMP1-AS1 was determined by quantitative reverse-transcription polymerase chain reaction in OS samples, and its role in OS was investigated by performing Cell Counting Kit-8, EdU, and Transwell assays. The characterization of exosomes derived from OS cell lines was conducted by transmission electron microscopyand Western blotting of CD9 and CD81. The effects of exosomes and exosomal SCAMP1-AS1 on OS cells were also evaluated in a series of cell assays. Furthermore, key molecules in the liver kinase B1-adenosine monophosphate-activated protein kinase (LKB1-AMPK) signaling pathway were analyzed by through Western blotting. The results revealed high SCAMP1-AS1 expression in OS, and its silencing in OS cells led to a reduction in cell proliferation, migration, and invasion. The OS cell-derived-exosomes increased the malignant characteristics in the target OS cell lines. Notably, exosomes obtained from OS cells in which SCAMP1-AS1 was silenced effectively counteracted the tumor-promoting effects typically observed with OS-derived exosomes on cocultured target OS cells by activating the LKB1-AMPK signaling pathway. These results demonstrate that exosomal SCAMP1-AS1 serves as a tumor promoter in OS by regulating the LKB1-AMPK signaling pathway.