The article describes the development of a program for the management and prevention of hand and foot skin reactions (HFSR) induced by targeted therapy. The goal was to build this program based on a systematic literature review and meta-analysis. Methods included article searches in databases such as CNKI, Embase, VIPbase, Wanfang, Cochrane Library, NGC, NCCN, NICE, SIGN and ESMO from inception to June 2023, followed by a two-round discussion of 10 experts. The final program contains 8 primary indicators, 16 secondary, 36 tertiary and 54 quaternary records. It includes a basic assessment of the skin of the hands and feet, care for erythema, keratosis, blisters, ulcers, pain management, management of other symptoms, and education about protection and prevention. The program is scientifically supported by evidence and expert discussions, clinically applicable and provides guidance for best practice. Personalized symptom management plans are recommended for early detection and relief of skin pain.