(1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were tested for IgM/IgG antibodies to the SARS-CoV-2 spike protein with the STANDARD™ Q COVID-19 IgM/IgG Plus Test (QNCOV-02C). ELISA/competitive inhibition ELISA (CI-ELISA) was subsequently run to assess the validity of the serological antibody test. (3) Results: The sensitivity of homeless people was 43.5%. The status of homelessness was related to a lower agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 0.35; 95% CI, 0.18–0.70). However, the Heterologous boost vaccine presented higher agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 6.50; 95% CI, 3.19–13.27). (4) Conclusions: This study found weak agreement between the rapid IgG results and confirmatory CI-ELISA testing in homeless people. However, it can be used as a screening test for the acceptance of homeless people with heterologous boost vaccination in facilities.