Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient’s adherence (mean treatment duration, 4.9 months; range 2–24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0–9 and 1; range 0–5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO2 laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.