Background The phenomenon of healthcare and social struggles among sex workers in communities of South Africa is a critical concern. Sex workers are often stigmatised, discriminated against, and violated. This study stems from the observation that sex workers experience daily healthcare and social challenges due to their line of work. This involves prejudice and stigma from the general public and medical professionals. Despite government efforts to raise the calibre of healthcare services, some healthcare systems remain problematic. Objective The study intended to critically review the publications on public health problems and barriers faced by sex workers. Methodology The systematic review methodology was used in the investigation. Identification of the problem, literature search, data evaluation, data analysis, and presentation were the five stages of the systematic review that were carried out. The following electronic databases were used to conduct a thorough search of the literature from 2013 to 2022: CINAHL, Medline, PubMed, JStore, and Embase. The search phrases included “sex workers,” “health problems,” “barriers,” “experiences,” “challenges,” “Mental Health,” and “systematic review”. Studies that were published prior to 2013 did not focus on the challenges, barriers, and social and health problems of sex workers and were not reported in English were excluded. Following the critical review evaluation, 30 studies were selected for this study out of a total of 85 studies. The categories were constructed using Creswell's Tesch method of data analysis. Results The analysis yielded two themes and seven subthemes: (1) public social problems that sex workers must navigate, including violence, criminalisation of sex work, stigma, prejudice, and linguistic and cultural hurdles, (2) high rates of HIV and STIs, a lack of comprehensive knowledge of reproductive and health issues, problems with mental health, and challenging access to care are some examples of the complexity of public healthcare. Conclusion A multipronged approach, including legal reform, destigmatisation, and increased access to healthcare and social support services, is required to address the healthcare and social struggles of sex workers.