The yield of solvent-tolerant cold active lipase from halo-tolerant Pseudomonas sp. VITCLP4 was improved by applying statistical methods to precisely combine medium components and other conditions. Two-level Plackett–Burman (PB) design was utilized to screen the most significant variables from a set of eleven variables that influence lipase production. Analysis of variance revealed that Tween-80, peptone, and KH2PO4 were statistically significant. Optimum levels of selected variables were ascertained by one-factor-at-a-time (OFAT) analysis. The optimum values and interactive effects of the selected three components were established by response surface methodology (RSM) based on the face-centered central composite design (FCCCD) using a three-level-three-factor approach. The optimized medium containing Tween-80, 0.5% (v/v), peptone, 0.75% (w/v), KH2PO4, 0.05% (w/v), yeast extract, 0.1% (w/v), olive oil, 0.2% (v/v) and inoculum size, 0.2% (v/v) resulted in maximum lipase production of 1342 Units ml− 1 min− 1 with 7.8 fold increase in the yield. This study provides insights into enhancing the lipase production statistically with optimized resources that can be utilized in bioprocess studies and industrial applications.