diff --git a/spras/config/config.py b/spras/config/config.py
index ebf10faa..bc427ed6 100644
--- a/spras/config/config.py
+++ b/spras/config/config.py
@@ -15,6 +15,7 @@
 import copy as copy
 import functools
 import itertools as it
+import re
 import warnings
 from pathlib import Path
 from typing import Any
@@ -28,6 +29,15 @@
 from spras.config.util import AlgorithmName, get_valid_algorithm_names
 from spras.util import LoosePathLike, NpHashEncoder, hash_params_sha1_base32
 
+# Modify YAML float specification when a YAML file is parsed directly
+# Default requires decimal point for scientific notation: https://yaml.org/type/float.html
+# add_implicit_resolver adds the regex pattern to the float type: https://pyyaml.org/wiki/PyYAMLDocumentation
+yaml.SafeLoader.add_implicit_resolver(
+    'tag:yaml.org,2002:float',
+    re.compile(r'^[-+]?([0-9]+(\.[0-9]*)?|\.[0-9]+)[eE][-+]?[0-9]+$'),
+    list('-+0123456789.')
+)
+
 config = None
 
 # This will get called in the Snakefile, instantiating the singleton with the raw config
@@ -39,6 +49,24 @@ def init_from_file(filepath):
     global config
     config = Config.from_file(filepath)
 
+def sanitize_scientific_notation(data: Any) -> Any:
+    """
+    Recursively checks a YAML configuration file parsed externally by Snakemake to convert scientific notation strings
+    back to floats.
+
+    Default YAML 1.1 requires decimal point for scientific notation: https://yaml.org/type/float.html
+    """
+    if isinstance(data, dict):
+        return {k: sanitize_scientific_notation(v) for k, v in data.items()}
+    elif isinstance(data, list):
+        return [sanitize_scientific_notation(item) for item in data]
+    elif isinstance(data, str):
+        if re.match(r'^[-+]?([0-9]+(\.[0-9]*)?|\.[0-9]+)[eE][-+]?[0-9]+$', data):
+            try:
+                return float(data)
+            except ValueError:
+                return data
+    return data
 
 class Config:
     def __init__(self, raw_config: dict[str, Any]):
@@ -47,6 +75,8 @@ def __init__(self, raw_config: dict[str, Any]):
         if raw_config == {}:
             raise ValueError("Config file cannot be empty. Use --configfile <filename> to set a config file.")
 
+        raw_config = sanitize_scientific_notation(raw_config)
+
         parsed_raw_config = RawConfig.model_validate(raw_config)
 
         # Member vars populated by process_config. Any values that don't have quick initial values are set to None
diff --git a/test/test_config.py b/test/test_config.py
index cf4cdf0f..d1b47936 100644
--- a/test/test_config.py
+++ b/test/test_config.py
@@ -3,6 +3,7 @@
 from typing import Iterable
 
 import pytest
+import yaml
 from pydantic import BaseModel
 
 import spras.config.config as config
@@ -451,3 +452,84 @@ def test_eval_summary_coupling(self, eval_include, summary_include, expected_eva
         assert config.config.analysis_include_evaluation == expected_eval
         assert config.config.analysis_include_summary == expected_summary
 
+
+    @pytest.mark.parametrize("numeric_string, expected_float", [
+        (".5", 0.5),
+        ("6.", 6.0),
+        ("3.1", 3.1),
+        ("-4.7", -4.7),
+        ("1e-3", 0.001),
+        ("1E-3", 0.001),
+        ("2.5e4", 25000.0),
+        ("2e4", 20000.0),
+        ("+5e+2", 500.0),
+        ("-3e-2", -0.03),
+    ])
+    def test_scientific_notation_variants(self, numeric_string, expected_float):
+        """
+        Ensures that the PyYAML SafeLoader accurately converts all standard
+        scientific notation formats into Python floats.
+        Used for YAML files parsed directly.
+        """
+        yaml_string = f"value: {numeric_string}"
+        # Tests the modified float imported from spras.config.config
+        parsed = yaml.safe_load(yaml_string)
+
+        assert isinstance(parsed["value"], float)
+        assert parsed["value"] == expected_float
+
+
+    @pytest.mark.parametrize("non_numeric_string", [
+        "range1e3",
+        "e-3",  # Missing coefficient
+        "1e",  # Missing exponent power
+    ])
+    def test_scientific_notation_does_not_match_strings(self, non_numeric_string):
+        """
+        Ensures that strings, labels, and parameters containing 'e' numbers
+        are correctly preserved as strings and not warped into floats.
+        Used for YAML files parsed directly.
+        """
+        yaml_string = f"label: {non_numeric_string}"
+        # Tests the modified float imported from spras.config.config
+        parsed = yaml.safe_load(yaml_string)
+
+        assert isinstance(parsed["label"], str)
+        assert parsed["label"] == non_numeric_string
+
+    def test_sanitize_scientific_notation(self):
+        """
+        Verifies that sanitize_scientific_notation recursively converts scientific
+        notation strings into floats across nested dictionaries and lists.
+        Used for YAML files loaded externally by Snakemake.
+        """
+        # Does not follow the SPRAS config file syntax
+        nested_config = {
+            "f": "1e-3",
+            "algorithms": {
+                "omicsintegrator2": {
+                    "params": {
+                        "sweep": ["2.5e4", "5e-2"],
+                        "x": "-6e2"
+                    },
+                    "nodes": "terminals"
+                }
+            },
+            "threads": 4
+        }
+
+        expected_config = {
+            "f": 0.001,
+            "algorithms": {
+                "omicsintegrator2": {
+                    "params": {
+                        "sweep": [25000.0, 0.05],
+                        "x": -600.0
+                    },
+                    "nodes": "terminals"
+                }
+            },
+            "threads": 4
+        }
+
+        assert config.sanitize_scientific_notation(nested_config) == expected_config