Schinzel-Giedion Syndrome (SGS) is an ultra-rare, multisystem, genetic developmental disorder caused by gain-of-function pathogenic variants in the SETBP1 gene. No standard of care (SoC) recommendations currently exist. To assess expert opinion on SoC for individuals with SGS using a modified Delphi method. A multidisciplinary panel of 21 experts from the USA and Europe was assembled. Experts responded to a two-round questionnaire, with a subgroup participating in a virtual workshop, through which recommendations pertaining to the diagnosis, monitoring, treatment, and management of SGS were iteratively developed. Consensus was defined as ≥ 70% of respondents demonstrating agreement/disagreement with 6-point Likert scale questions, or ≥ 70% of respondents selecting a given multiple-choice question option. Overall, 81/94 statements achieved consensus. Experts agreed that the recommendations should be considered applicable to any individual with confirmed SGS or an indicative phenotype and any SETBP1 gain-of-function mutation. Key considerations included early and sustained involvement of a multidisciplinary team, routine monitoring for common tumors, neurologic, renal, genitourinary, pulmonary, musculoskeletal and gastrointestinal manifestations/complications, and facilitation of shared decision-making processes. These recommendations should help guide clinicians and families/caregivers in care decisions to enhance quality and duration of life for individuals with SGS and facilitate shared decision-making.