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Small and Medium Enterprises (SMEs) are crucial to Zambia’s economic growth but continue to face challenges in sustaining profitability. This study examined the effect of firm characteristics on SME profitability, aiming to (i) identify the most influential characteristic and (ii) analyse their relationships with profitability. The characteristics assessed included firm size, firm age, debt finance, liquidity, and sales growth. Data were collected from 270 SMEs registered with the Patents and Companies Registration Agency (PACRA) across seven urban centres: Livingstone, Lusaka, Kabwe, Ndola, Kitwe, Chingola, and Chililabombwe, using structured, face-to-face questionnaires. Systematic random sampling was employed, and data were analysed using factor analysis, Pearson correlation, regression, and Chi-square tests. Results showed that firm characteristics collectively have a significant effect on SME profitability, though individual relationships were weak and statistically insignificant. Among the characteristics, sales growth had the strongest influence. However, regression results (R² = 0.002, F = 0.237, p = 0.790) indicated very weak predictive power, suggesting that firm characteristics explain only 0.2% of profitability variance. This implies that SME profitability in Zambia is influenced by the combined interaction of factors rather than individual characteristics. The study contributes new insights by identifying sales growth as the most influential factor, highlighting that sales growth drives SME profitability even in resource-constrained contexts like Zambia. Policymakers should prioritise integrated strategies that foster sales growth through innovation, market diversification, and digital marketing, while enhancing liquidity through accessible, low-interest financing. Financial policy reforms should prioritize accessible, low-interest financing mechanisms that enhance liquidity and sustainable debt utilisation.