Background Serosurveillance can estimate the prevalence of antibodies (Ab) acquired through vaccination or current and/or past infection. Multi-pathogen serosurveillance that measures multiple Ab simultaneously, can enable identification of vulnerable sub-populations with immunity gaps to vaccine preventable diseases (VPD) and concurrent burden of neglected tropical disease (NTD), including those nearing elimination (lymphatic filariasis [LF], trachoma) and eradication (yaws). This study aimed to estimate seroprevalence and identify temporal trends of selected VPDs and NTDs in Samoa to inform targeted public health action. Methodology/Principal Findings Dried blood spots were collected from four repeated community-based surveys in eight primary sampling units (PSU) in Samoa in 2018, 2019, 2023 and 2024. Multiplex bead assays were used to detect Abs against antigens (Ag) for diphtheria, measles, rubella, tetanus, LF [Wb123 or Bm14], yaws [both Rp17 and TmpA;