The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges regarding the oral administration of medicine to inpatients in a variety of healthcare settings such as (1) hospitals, (2) nursing homes and (3) long-term stay units (LTSUs). A literature search was undertaken in September 2021 and repeated in June 2023 in the following databases: PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, PsycINFO and ProQuest. A Microsoft Excel® spreadsheet was devised to collate the following data from each eligible study: study author and year, country, number of participants, title, duration (follow-up period), study design, inclusion and exclusion criteria, method and data collection, relevant outcomes, and key findings. A total of 3023 records were identified, with 12 articles being included in the final systematic review. Seven of the twelve studies reported on the prevalence of difficulties swallowing SODFs, which varied from 10–34.2%. Nine of the twelve studies reported the methods used to manipulate SODFs, with the most reported method being tablet crushing. Given the prevalence of swallowing difficulties and the subsequent crushing of medicines in response to this, it is evident that concerns should be raised regarding the potential for a medication administration error to occur.</p