Non-performing loans (NPLs) are significantly influenced by macroeconomic and microeconomic determinants and, in turn, the NPLs have a profound impact on the banking sector. The intricate relationship between NPLs and these determinants affects key banking metrics such as returns to scale, cost efficiency, and operational effectiveness. This chapter critically explores the relationship between NPLs and key macroeconomic indicators, including Gross Domestic Product (GDP), inflation, unemployment rates, exchange rates, and interest rates. Through a comprehensive review of global research studies conducted in various socio-economic contexts, this chapter offers a thorough examination of how these variables interact with NPLs. To substantiate the analysis, a data series covering 13 years (from 2008 to 2020) was used to analyse the trend of these variables in the UK, India and Ireland. In addition, statistical tools such as the mean, correlation coefficients, and standard deviation were applied to understand the dynamics between NPLs and these macroeconomic determinants. The findings are further enhanced by a comparative analysis, offering a unique and insightful perspective on the subject area.