Shikonin (SKN), a naturally occurring naphthoquinone derived mainly from the roots of Lithospermum erythrorhizon Siebold & Zucc., has emerged as a promising anticancer agent against lung cancer. Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, primarily due to aggressive progression, metastasis, and resistance to conventional therapies. The phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in NSCLC development, survival, and therapeutic resistance, making it an attractive molecular target. This literature review was conducted through a systematic search of PubMed, Scopus, Web of Science, and Google Scholar for studies published between January 2010 and December 2024. In vitro, in vivo, and available clinical studies evaluating the anticancer effects of SKN in lung cancer models were included, with particular emphasis on modulation of the PI3K-AKT-mTOR pathway. Relevant data were extracted and qualitatively synthesized to summarize molecular mechanisms, pharmacokinetic (PK) characteristics, toxicological profiles, and clinical relevance. The collected evidence demonstrates that SKN effectively inhibits PI3K, AKT, and mTOR signaling, leading to apoptosis induction, suppression of tumor cell proliferation, inhibition of epithelial–mesenchymal transition, and reduced metastatic potential. Additionally, SKN shows efficacy against chemoresistant lung cancer cells and enhances the response to standard anticancer therapies. Although preclinical and limited clinical findings are encouraging, further well-designed clinical trials are required to establish safety, optimize dosing, and validate combination treatment strategies. Overall, SKN represents a promising natural candidate for targeted NSCLC therapy.