Active Pharmaceutical Ingredients (APIs) in the aquatic environment have become a growing concern due to their potential health and environmental impacts. The review aims to examine the occurrence and removal efficiency of APIs in the influent and effluent of wastewater treatment plants (WWTPs) in Southeast Asian countries, including Thailand, Singapore, Malaysia, Indonesia, Vietnam, and the Philippines. The review covers five classes of APIs, i.e., nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, anticonvulsants, antihypertensives, and stimulants. We systematically scoured Scopus-indexed articles published from 2011 to 2022 from Google Scholar, PubMed, and Dimensions and extracted measured concentrations of APIs detected in WWTPs. The wastewater influent contained the following APIs from each class in the highest mean or median concentrations: paracetamol (mean: 26,000 ng/L), ciprofloxacin (mean: 567.4 ng/L), gabapentin (median: up to 3609 ng/ L), atenolol (median: up to 4124 ng/L), and caffeine (mean: 38,000 ng/L). Moreover, studies in Singapore have recorded the highest treatment efficiency on various APIs compared to those recorded in Malaysia, Thailand, or Vietnam. This study underscores the importance of implementing standardized monitoring techniques, enhancing wastewater infrastructure, and raising awareness among parties involved to address the environmental hazards linked to pharmaceutical pollution effectively.